Offspring Adiposity Research Articles

Association of maternal obesity and gestational diabetes mellitus with overweight/obesity and fatty liver risk in offspring

BACKGROUNDChildhood obesity and fatty liver are associated with adverse outcomes such as diabetes, metabolic syndrome, and cardiovascular diseases in adulthood. It is very important to identify relevant risk factors and intervene as early as possible. At present, the relationship between maternal and offspring metabolic factors is conflicting.AIMTo estimate the association of maternal obesity and gestational diabetes mellitus (GDM) with overweight/obesity and fatty liver risk in offspring at 8 years of age.METHODSThe prospective study included mothers who all had a 75-g oral glucose tolerance test at 24-28 wk of gestation and whose offspring completed follow-up at 8 years of age. Offspring birth weight, sex, height, weight, and body mass index (BMI) were measured and calculated. FibroScan-502 examination with an M probe (Echosens, Paris, France) was prospectively conducted in offspring aged 8 years from the Shanghai Prenatal Cohort Study.RESULTSA total of 430 mother-child pairs were included in the analysis. A total of 62 (14.2%) mothers were classified as obese, and 48 (11.1%) were classified as having GDM. The mean age of the offspring at follow-up was 8 years old. Thirty-seven (8.6%) offspring were overweight, 14 (3.3%) had obesity, and 60 (14.0%) had fatty liver. The prevalence of overweight, obesity and fatty liver in offspring increased significantly across maternal BMI quartiles (all P < 0.05). Among offspring of mothers with GDM, 12 (25.0%) were overweight, 4 (8.3%) were obese, and 12 (25.0%) had fatty liver vs. 25 (6.5%), 10 (2.6%) and 48 (12.6%), respectively, for offspring of mothers without GDM (all P < 0.05). In multiple logistic regression, after adjustment for variables, the OR for fatty liver in offspring was 8.26 (95%CI: 2.38-28.75) for maternal obesity and GDM.CONCLUSIONThis study showed that maternal obesity can increase the odds of overweight/obesity and fatty liver in offspring, and GDM status also increases the odds of overweight/obesity in offspring. Weight management and glycemic control before and during pregnancy need to be highlighted in primary prevention of pediatric obesity and fatty liver.

Predicting the earliest deviation in weight gain in the course towards manifest overweight in offspring exposed to obesity in pregnancy: a longitudinal cohort study

BackgroundObesity in pregnancy and related early-life factors place the offspring at the highest risk of being overweight. Despite convincing evidence on these associations, there is an unmet public health need to identify “high-risk” offspring by predicting very early deviations in weight gain patterns as a subclinical stage towards overweight. However, data and methods for individual risk prediction are lacking. We aimed to identify those infants exposed to obesity in pregnancy at ages 3 months, 1 year, and 2 years who likely will follow a higher-than-normal body mass index (BMI) growth trajectory towards manifest overweight by developing an early-risk quantification system.MethodsThis study uses data from the prospective mother-child cohort study Programming of Enhanced Adiposity Risk in CHildhood–Early Screening (PEACHES) comprising 1671 mothers with pre-conception obesity and without (controls) and their offspring. Exposures were pre- and postnatal risks documented in patient-held maternal and child health records. The main outcome was a “higher-than-normal BMI growth pattern” preceding overweight, defined as BMI z-score >1 SD (i.e., World Health Organization [WHO] cut-off “at risk of overweight”) at least twice during consecutive offspring growth periods between age 6 months and 5 years. The independent cohort PErinatal Prevention of Obesity (PEPO) comprising 11,730 mother-child pairs recruited close to school entry (around age 6 years) was available for data validation. Cluster analysis and sequential prediction modelling were performed.ResultsData of 1557 PEACHES mother-child pairs and the validation cohort were analyzed comprising more than 50,000 offspring BMI measurements. More than 1-in-5 offspring exposed to obesity in pregnancy belonged to an upper BMI z-score cluster as a distinct pattern of BMI development (above the cut-off of 1 SD) from the first months of life onwards resulting in preschool overweight/obesity (age 5 years: odds ratio [OR] 16.13; 95% confidence interval [CI] 9.98–26.05). Contributing early-life factors including excessive weight gain (OR 2.08; 95% CI 1.25–3.45) and smoking (OR 1.94; 95% CI 1.27–2.95) in pregnancy were instrumental in predicting a “higher-than-normal BMI growth pattern” at age 3 months and re-evaluating the risk at ages 1 year and 2 years (area under the receiver operating characteristic [AUROC] 0.69–0.79, sensitivity 70.7–76.0%, specificity 64.7–78.1%). External validation of prediction models demonstrated adequate predictive performances.ConclusionsWe devised a novel sequential strategy of individual prediction and re-evaluation of a higher-than-normal weight gain in “high-risk” infants well before developing overweight to guide decision-making. The strategy holds promise to elaborate interventions in an early preventive manner for integration in systems of well-child care.

Relationship between Gestational Weight Gain Rate Trajectory and Overweight in Offspring at Three Years of Age.

Background: The incidence of childhood obesity has increased rapidly, and its relationship with adult diseases is constantly being revealed. Maternal factors have been shown to play an important role in the growth and development of newborns. In this article, we explored the relationship between the gestational weight gain (GWG) rate and overweight/obesity in offspring at 3 years of age. Methods: A total of 5146 pregnant women and their children registered between January 2010 and December 2018 were studied by a retrospective cohort study. The Group-based Trajectory Model was used to distinguish the GWG rate patterns. Overweight/obesity was diagnosed by the weight-for-height Z-score at 3 years of age. Logistic regression was used to analyze the association between GWG rate patterns and outcomes. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to analyze the association between GWG rate patterns and overweight/obesity in offspring at 3 years of age. Results: Three GWG rate growth patterns were identified in this study. The incidence of offspring overweight/obesity in the low-stable, high-stable, and low-sharp patterns was 8.33%, 3.68%, and 6.03% respectively. After adjusting covariates, compared with the low-stable pattern, the high-stable pattern increased the risk for offspring to be overweight/obesity at 3 years of age, with OR of 2.26 (95% CI, 1.31-3.90). However, the low-sharp pattern was not associated with overweight/obesity in offspring at 3 years of age. Conclusions: The high-stable increasing pattern of the GWG rate is a risk factor for overweight/obesity in offspring at 3 years of age.

Maternal serum adipokines and inflammatory markers at late gestation and newborn weight in mothers with and without gestational diabetes mellitus.

Maternal obesity increases the risk of gestational diabetes mellitus (GDM) and is positively correlated with neonatal obesity increasing the risk of adiposity in both young and adult offspring. Maternal secreted factors from adipose tissue such as adipokines and inflammatory cytokines may regulate fetal growth. This study investigated associations between maternal adipokines and inflammatory markers at late gestation, and neonatal anthropometric characteristics in mothers with and without GDM. The study included 65 women with GDM and 65 pregnant women with normal glucose tolerance evaluated at the time of term elective Caesarean section. Adiponectin, leptin, resistin, adipsin, neutrophil gelatinase-associated lipocalin (NGAL), nerve growth factor (NGF), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured in maternal serum by the multiplex immunoassay using Magpix technology. C-reactive protein (CRP) was measured with a particle-enhanced turbidimetric immunoassay and neonatal anthropometric variables were assessed. The association of birthweight with individual biomarkers was analyzed using multivariate logistic regression adjusted for maternal factors. Adiponectin, leptin, resistin, adipsin, NGAL and NGF were not significantly associated with higher birthweight. The maternal factors in association with higher birthweight observed in GDM were CRP, MCP-1 and TNF-alpha levels. Regression analysis showed that TNF-alpha was an independent risk factor for higher birthweight (p = 0.046). These results suggest an involvement of maternal inflammatory markers at late gestation and fetal growth in mothers with GDM, and that TNF-alpha could play a major role.

Feeding Patterns, Mother-Child Dietary Diversity and Prevalence of Malnutrition Among Under-Five Children in Lebanon: A Cross-Sectional Study Based on Retrospective Recall

BackgroundDespite demonstrated benefits, most countries fall short of meeting international targets for breastfeeding patterns, optimal complementary feeding, mother-children's quality diet, and malnutrition among under-five children.RationaleSince mothers usually play the most vital role in the healthcare of their children, research is needed to illuminate maternal factors that might promote a child's health and nutritional status.AimThe purpose of this study is to retrospectively (1) examine the under-five children's (0–59 months) feeding habits including exclusive breastfeeding, exclusive bottle feeding, continued breastfeeding, and complementary feedings, (2) investigate the mother-child's dietary diversity, and (3) identify any factors that cause less optimal nutrition due to a lack of food diversity in children aged 6 to 59 months. Moreover, (4) the prevalence of wasting, stunting, underweight, and overweight in the under-five offspring living in households located in the main two provinces in Lebanon (Beirut and Mount Lebanon) was determined.MethodsThe data for this analysis were collected from a representative sample of 384 households [384 mothers (21–49 years old) and children (0–59 months)] between February 2019 and June 2019. A questionnaire was used to inquire mothers of children ages 0–23 months about exclusive breastfeeding (EBF), continuous breastfeeding (CBF), exclusive bottle feeding (EBOT), mixed feeding (MF), and complementary feeding patterns. Moreover, additional questions regarding dietary diversity were asked to mothers of children aged 6 to 59 months. This score was calculated based on the 24 h recall of the mother and her child's consumption of 7 food groups, during the 24 h prior to the survey. Moreover, stunting, wasting, overweight, and underweight were calculated using the z-score for height-for-age (HAZ), weight-for-height (WHZ), and weight-for-age (WAZ), respectively. Binary logistic regression was used to explore the dietary diversity among children (ages 6–59 months) adjusting for covariates at maternal and household levels.ResultsAround 44% of children (0–59 months) had normal body weight. In addition, 9.3% were underweight (WAZ < -2SD to −3SD), 6.5% were at risk of being overweight, 24.45% were overweight, 9.3% were stunted (HAZ < -2SD to −3SD), and 6.25% (WHZ < -2SD to −3SD) were wasted. In total, among under-five children, the prevalence of EBF at 40 d and 6 months was 27 and 30%, respectively. The prevalence of CBF was 23%. Around 60% of mothers breastfed their offspring between 0 and 6 months and half of them introduced infant formula at earlier stages between 0–6 months. Furthermore, 78.4% of mothers introduced food to their children between 4 and 6 months (of which 40% before 6 months) and 62.5% of them introduced sugary drinks before 6 months. As for dietary diversity (DD), one out of two mothers and one out of three children (ages 6–59 months) had a low DD score (DDS) (46 and 32%, respectively). The children's and mother's DD were strongly found to be correlated (p-value = 0.034). Regression analysis showed that children's DD increased around 2 times [AOR = 1.7; 95% CI (1.042–2.914)] in context of high maternal DDS, and about 12 times [AOR = 11.7; 95% CI (1.2–111)] when a member of the highest-income households.ConclusionsOur findings demonstrated low rates of EBF and CBF, high prevalence of EBOT, and early introduction of complementary foods among children ages 0–59 months. Furthermore, for children ages 6–59 months, there was poor mother-child dietary diversity and a high prevalence of overweight and stunted children in the main two Lebanese provinces. This suggests the alarming need for continuous nutrition intervention to improve infant feeding patterns and dietary diversity to reduce the malnutrition rates.

Maternal exercise and high-fat diet affect hypothalamic neural projections in rat offspring in a sex-specific manner

This study aimed to investigate the effect of maternal high-fat (HF) diet and exercise during gestation and lactation on hypothalamic neural projection development in the offspring. Pregnant Sprague-Dawley rats were fed a CHOW or HF diet during gestation and lactation, and further divided into two subgroups: voluntary exercised and sedentary. Offspring's brains and tissue were collected at weaning and 16 weeks of age. Maternal exercise downregulated dams’ body weight and food intake during lactation, but failed to normalize increased fat weight, plasma and milk leptin levels of HF dams at weaning. Maternal HF diet significantly increased offspring's body weight, adipose depots, plasma insulin, and leptin at weaning and had long-term effect on body weight of male offspring, while maternal exercise decreased offspring's body weight from 3 to 5 weeks of age in both sexes. At weaning, maternal exercise decreased αMSH fiber density and maternal HF diet impaired agouti-related peptide fiber density in the paraventricular nucleus of hypothalamus of male pups, while maternal HF diet disrupted αMSH fiber density in the paraventricular nucleus of hypothalamus of female pups. The impaired αMSH fiber density was consistent with reduced STAT3 signaling in the arcuate nucleus of hypothalamus, while the reduced agouti-related peptide fiber density was consistent with reduced ERK1/2 signaling in the arcuate nucleus of hypothalamus. The impaired hypothalamic projections were compensated in adulthood in both sexes. Our findings suggest that maternal HF diet and exercise exerts different effects on hypothalamic neural projections development through distinct signaling pathways in a sex-specific manner.

Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores

BackgroundGreater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal.MethodsWe undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10–18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs).ResultsMV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (Pdifference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size.ConclusionsOur results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age.

Abstract 165: Age-specific Effects Of Maternal Gut Biome Influence Sex Dependent Changes In Offspring Weight, Behavior, And Depression

Background: The gut-brain axis has recently become key in understanding stroke pathogenesis. The bidirectional communication between the gut and the brain are highly involved in the immune response to stroke. The effect of the aged biome, naturally occurring dysbiosis through the process of inflammaging, may have significant impact on offspring in terms of stroke risk factors. Method: Young (3-month) female wildtype C57B/6 mice were subjected to antibiotic treatment to clear their native gut biome and were then treated with fecal microbiome transplants from 3-month (M) control, 14M menopausal, and 18M reproductively senescent female mice, and were bred in our facility. Subsequent pups obtained were aged to 9 months followed by a battery of behavioral tests (novel object recognition (NORT), Y-maze, tail suspension, and open field test) and body weight measurements. Feces was collected periodically for 16s rRNA sequencing analysis. Results: Aged biome affected the female fecundity significantly (p=0.028, n=7/12) and the pup biome showed a significant sex specific difference in composition through 16s sequencing (p=0.009, n=7). Female pup from 14- or 18M biome mothers had consistently higher body weight from 21 days to 9 months of age compared to controls (p=0.183, n=6/9/13). Male pups from 18M biome dams showed significantly low body weight 2 months post birth (p=0.048, n= 7/10). Mothers that received 14M biome had overweight male offspring at 9 months of age (p=0.017. Cognitive assessment through NORT showed that female pups from mothers colonized with 14M biome had a significantly lower discrimination index compared to controls (p=0.045, n=6/9). Only male pups from 14M biome mothers showed a deficit in spatial cognition (p=0.018). Both males and females exhibited an early depressive phenotype compared to controls at 2 months of age (p=0.028), with female pups also exhibiting this phenotype at 9 months (p=0.018). Conclusion: Age of the maternal biome has a significant effect on its offspring’s health, specifically body weight, cognition, and depressive phenotype in a sex and time dependent manner. These effects correlate positively with stroke risk factors highlighting the importance of the microbiome as an epigenetic regulator of offspring health.

Gut microbiota mediates the alleviative effect of polar lipids-enriched milk fat globule membrane on obesity-induced glucose metabolism disorders in peripheral tissues in rat dams.

Obesity during pregnancy and lactation not only increases the incidence of metabolic disorders and gestational diabetes in mothers, but also programs adiposity and related metabolic diseases in offspring. The aim of this study was to investigate the effects of milk polar lipids on gut microbiota and glucose metabolism in high-fat diet (HFD)-fed rat dams. Sprague Dawley (SD) female rats were fed a HFD for 8 weeks to induce obesity, followed by HFD with or without oral administration of polar lipids-enriched milk fat globule membrane (MFGM-PL) at 400 mg/kg BW during pregnancy and lactation. At the end of lactation, fresh fecal samples of dams were collected, the gut microbiota was assessed, and the insulin-signaling protein expression in peripheral tissues (adipose tissue, liver and skeletal muscle) were measured. MFGM-PL supplementation attenuated body weight gain, ameliorated serum lipid profiles and improved insulin sensitivity in obese dams at the end of lactation. 16 S rDNA sequencing revealed that MFGM-PL increased the community richness and diversity of gut microbiota. The composition of gut microbiota was also changed after MFGM-PL supplementation as shown by an increase in the ratio of Bacteroidetes/Firmicutes and the relative abundance of Akkermansia, as well as a decrease in the relative abundance of Ruminococcaceae. The functional prediction of microbial communities by PICRUSt analysis showed that there were 7 KEGG pathways related to carbohydrate metabolism changed after MFGM-PL supplementation to HFD dams, including glycolysis/gluconeogenesis and insulin signaling pathway. Furthermore, MFGM-PL improved insulin signaling in the peripheral tissues including liver, adipose tissue and skeletal muscle. MFGM-PL supplementation during pregnancy and lactation improves the glucose metabolism disorders in HFD-induced obese dams, which may be linked to the regulation of gut microbiota induced by MFGM-PL.

Metabolic programming in the offspring after gestational overfeeding in the mother: toward neonatal rescuing with metformin in a swine model.

Maternal overfeeding during gestation may lead to adverse metabolic programming in the offspring mediated by epigenetic alterations. Potential reversal, in early life, of these alterations may help in the prevention of future cardio-metabolic conditions. In this context, our aims were: (1) to study the effects of maternal overfeeding on the metabolic and epigenetic programming of offspring's adipose tissue; and (2) to test the potential of postnatal metformin treatment to reverse these changes. We used a swine animal model where commercial production sows were either overfed or kept under standard diet during gestation, and piglets at birth were randomly assigned to metformin (n = 16 per group) or vehicle treatment during lactation (n = 16 per group). Piglets born to overfed sows showed a worse metabolic profile (higher weight, weight gain from birth and abdominal circumference; all p < 0.05) together with altered serological markers (increased HOMA-IR, fructosamine, total cholesterol, C-Reactive Protein and lower HMW adiponectin; all p < 0.05). The visceral adipose tissue also showed altered morphology (increased adipocyte area, perimeter and diameter; all p < 0.05), as well as changes in gene expression (higher CCL2 and INSR, lower DLK1; all p < 0.05), and in DNA methylation (96 hypermethylated and 99 hypomethylated CpG sites; FDR < 0.05). Metformin treatment significantly ameliorated the abnormal metabolic profile, decreasing piglets' weight, weight gain from birth, abdominal circumference and fructosamine (all p < 0.05) and reduced adipocyte area, perimeter, and diameter in visceral adipose tissue (all p < 0.05). In addition, metformin treatment potentiated several associations between gene expression in visceral adipose tissue and the altered metabolic markers. Maternal overfeeding during gestation leads to metabolic abnormalities in the offspring, including adipose tissue alterations. Early metformin treatment mitigates these effects and could help rescue the offspring's metabolic health.

Maternal hyperandrogenism is associated with a higher risk of type 2 diabetes mellitus and overweight in adolescent and adult female offspring: a long-term population-based follow-up study

Adverse intrauterine environment may predispose offspring to cardio-metabolic dysfunction in later life. In this study, we aimed to investigate the effects of maternal hyperandrogenism (MH) on cardio-metabolic risk factors in female offspring in later life. This prospective population-based study included 211 female offspring with MH and 757 female offspring without MH (controls). Both groups were followed from baseline to the date of incidence of events, censoring, or end of the study period, whichever came first. Age scaled unadjusted and adjusted cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association of MH with pre-diabetes (pre-DM), type 2 diabetes mellitus (T2DM), overweight and obesity in offspring of both groups. Statistical analysis was performed using the software package STATA; significance level was set at P < 0.05. This study revealed a higher risk of T2DM (unadjusted HR 2.67, 95% CI 1.33-5.36) and overweight (unadjusted HR 1.41, 95% CI 1.06-1.88) in female offspring with MH, compared to controls. Results remained unchanged after adjustment for potential confounders including body mass index, education, physical activity, mother's age at delivery, birth weight, and childhood obesity. However, no significant difference was observed in the risk of pre-DM and obesity in females with MH, compared to controls in both unadjusted and adjusted models. This pioneer study with a long-term follow-up demonstrated that MH increases the risk of developing T2DM and being overweight in female offspring in later life. Further long-term population-based studies are needed to confirm these findings.

Dietary interventions in mice affect oxidative stress and gene expression of the Prlr and Esr1 in the adipose tissue and hypothalamus of dams and their offspring.

Maternal diet is key to the progeny's health since it may impact on the offspring's adult life. In this study, mice dams received standard (CONT), restrictive (RD), or hypercaloric (HD) diets during mating, pregnancy, and lactation. Male offspring of each group of dams also received these diets: CONT, RD, HD. Aiming to evaluate the oxidative stress in the adipose tissue, reactive oxygen species (ROS) production, catalase (CAT), and superoxide dismutase (SOD) activities were analyzed in dams and offspring. In the adipose tissue and hypothalamus, gene expression of prolactin (Prlr) and estrogen alpha (Esr1) receptors was performed in dams and offspring. Protein expression of Stat5 was evaluated in the adipose tissue of the offspring from RD-fed dams. HD-fed dams increased triglycerides and leptin serum concentrations, and decreased SOD activity in the adipose tissue. In the offspring's adipose tissue, we observed a maternal diet effect caused by HD, with increased ROS production and SOD and CAT activities. Gene expression of Prlr and Esr1 in the offspring's adipose tissue was decreased due to maternal RD. Mice from HD-fed dams showed higher Stat5 expression compared to the offspring from CONT and RD dams in the adipose tissue. In the hypothalamus, we found decreased expression of Prlr in RD and HD dams, compared to CONT; and a maternal diet effect on Prlr and Esr1 gene expression in the offspring. In conclusion, we can affirm that maternal nutrition impacts the redox state and influences the gene expression of Prlr and Esr1, which are involved in energy metabolism, both peripherally and centrally in the adult life of the female offspring.

Immune Cell and Adipose Gene Expression Reprogramming in Juvenile Monkeys Born to Health and Weight-Diverse Mothers

Over 93 million Americans are obese and 66 million suffer from metabolic disease. Roughly 40% of obese people do not have metabolic abnormalities (metabolically health obese [MHO]), while approximately 15% of lean do (metabolically unhealthy lean [MUL]). African green monkeys (AGMs) demonstrate naturally occurring obesity and metabolic syndrome (MetS) without diet manipulation, and MetS criteria are heritable. Age-matched maternal AGMs were classified by adjusted MetS criteria ([n=44]; waist >40cm, fasting glucose (FG) >100 mg/dL, SBP/DBP >135/85mmHg, and HDL-c <50mg/dL) and classified as metabolically healthy lean (MHL), MHO, MUL or metabolically unhealthy obese (MUO). Age, weight and sex-matched pre-pubertal juvenile offspring from these mothers were additionally selected (n=9-11/group; ages=1.1-3.4years) for evaluation. We assessed monocyte subtypes by flow cytometry, and subcutaneous adipose gene expression patterns by RNAseq. Non-classical monocytes were increased in obese and unhealthy mothers (MHO p=0.02, MUL p=0.003, MUO p=0.00002) compared to MHL. MUL and MUO juvenile offspring also had more non-classical monocytes compared to MHL (p=0.05 and p=0.07). Monocyte chemoattractant protein-1 (MCP)-1 was measured in plasma and found to be elevated in MUO juveniles (p=0.02). Patterns of increased cytokine and extracellular matrix gene expression were seen in MUL and MUO juveniles’ adipose (6-7/group), mirroring obese and unhealthy mothers’ adipose gene expression patterns. Maternal health and obesity influence offspring immune cells and adipose gene expression prior to weight gain and metabolic disease onset. Our data underscore maternal monocyte and adipose profiles as inherited phenotypes that present prior to adipose expansion and may be targets to improve intergenerational health trajectories.

Longitudinal dietary trajectories from preconception to mid-childhood in women and children in the Southampton Women\u2019s Survey and their relation to offspring adiposity: a group-based trajectory modelling approach

BackgroundRates of childhood obesity are increasing globally, with poor dietary quality an important contributory factor. Evaluation of longitudinal diet quality across early life could identify timepoints and subgroups for nutritional interventions as part of effective public health strategies.ObjectiveThis research aimed to: (1) define latent classes of mother-offspring diet quality trajectories from pre-pregnancy to child age 8–9 years, (2) identify early life factors associated with these trajectories, and (3) describe the association between the trajectories and childhood adiposity outcomes.DesignDietary data from 2963 UK Southampton Women’s Survey mother-offspring dyads were analysed using group-based trajectory modelling of a diet quality index (DQI). Maternal diet was assessed pre-pregnancy and at 11- and 34-weeks’ gestation, and offspring diet at ages 6 and 12 months, 3, 6-7- and 8–9-years using interviewer-administered food frequency questionnaires. At each timepoint, a standardised DQI was derived using principal component analysis. Adiposity age 8–9 years was assessed using dual-energy X-ray absorptiometry (DXA) and BMI z-scores.ResultsA five-trajectory group model was identified as optimal. The diet quality trajectories were characterised as stable, horizontal lines and were categorised as poor (n = 142), poor-medium (n = 667), medium (n = 1146), medium-better (n = 818) and best (n = 163). A poorer dietary trajectory was associated with higher maternal pre-pregnancy BMI, smoking, multiparity, lower maternal age and lower educational attainment. Using linear regression adjusted for confounders, a 1-category decrease in the dietary trajectory was associated with higher DXA percentage body fat (0.08 SD (95% confidence interval 0.01, 0.15) and BMI z-score (0.08 SD (0.00, 0.16) in the 1216 children followed up at age 8–9 years.ConclusionMother-offspring dietary trajectories are stable across early life, with poorer diet quality associated with maternal socio-demographic and other factors and childhood adiposity. The preconception period may be an important window to promote positive maternal dietary changes in order to improve childhood outcomes.

The Relationship Between Paternal Preconception Obesity and Health Behaviors and Childhood Obesity: Protocol for a Systematic Review.

BackgroundChildhood obesity is a global public health concern and is a priority for researchers and policy makers. To overcome the epidemic of obesity, influencing factors throughout the life span need to be addressed, including those in the preconception period. A better understanding of the association between paternal preconception factors and childhood obesity is important for public health interventions.ObjectiveThis systematic review will examine the relationship between paternal preconception obesity and health behaviors and their offspring’s overweight or obesity.MethodsPeer-reviewed quantitative studies and grey literature that report associations between paternal preconception obesity and health behaviors—such as smoking, exercise, and eating habits—and childhood overweight and obesity will be identified through a computerized literature search in 7 databases. The quality of each study will be assessed using the Quality Assessment Tool for Quantitative Studies. Characteristics of the included studies will be reported, and relevant findings from each paternal preconception exposure will be narratively synthesized. This review will follow the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines.ResultsThis systematic review is anticipated to begin in December 2021 and be completed by the end of August 2022.ConclusionsThis systematic review will contribute to a better understanding of the relationship between preconception paternal exposures and their offspring’s overweight or obesity. Findings will help support health professionals working with prospective parents to educate fathers on the benefits of improving their weight and health behaviors during the preconception period.International Registered Report Identifier (IRRID)PRR1-10.2196/31254

Fructooligosaccharide ameliorates high-fat induced intrauterine inflammation and improves lipid profile in the hamster offspring

Maternal high-fat diet (HFD) often results in intrauterine and feto-placental inflammation, and increases the risks of fetal programming of metabolic diseases. Intake of prebiotic is reported beneficial. However, its effects on HFD during pregnancy and lactation is not known. We evaluated the maternal intake of fructooligosaccharide (FOS) and its impact on placental inflammation, offspring's adiposity, glucose, and lipid metabolism in their later life. Female Golden Syrian hamsters were fed with a control diet (CD, 26.4 % energy from fat) or HFD (60.7% energy from fat) in the presence or absence of FOS from preconception until lactation. All pups were switched over to CD after lactation and continued until the end. Placental inflammation was upregulated in HFD-fed dam, as measured by a high concentration of hsCRP in the serum and amniotic fluid. Neutrophil infiltration was significantly increased in the decidua through the chorionic layer of the placenta. The expression of pro-inflammatory cytokines such as COX2, NFκβ, IL-8, TGFβ mRNA was increased in the chorioamniotic membrane (P <.05). The HFD/CD hamsters had more adiposity, higher triglyceride, and low HDL at 12 months of age compared to CD/CD (P <.05). However, HFD+FOS/CD-fed hamsters prevented adverse effects such as placental inflammation, neutrophil infiltration, glucose, and lipid profiles in the offspring (P <.05). Anti-inflammatory and lipid-lowering effects of FOS may reduce placental inflammation by lowering neutrophil infiltration and decreasing the production of pro-inflammatory cytokines. Intake of FOS during pregnancy may be beneficial in maintaining lipid metabolism and preventing excess adiposity for mother and their offspring.

Maternal carbohydrate intake during pregnancy is associated with child peripubertal markers of metabolic health but not adiposity.

To examine the associations of trimester-specific maternal prenatal carbohydrate (CHO) intake with offspring adiposity and metabolic health during peripuberty. Prospective cohort study in which maternal dietary intake was collected via validated FFQ during each trimester. Offspring adiposity and metabolic biomarkers were evaluated at age 8-14 years. We used multivariable linear regression to examine associations between total energy-adjusted maternal CHO intake and offspring BMI z-score, skinfold thickness and metabolic syndrome risk z-score calculated as the average of waist circumference, fasting glucose, fasting C-peptide, TAG:HDL and systolic blood pressure + diastolic blood pressure/2. Mexico City, Mexico. 237 mother-child pairs in the Early Life Exposure in Mexico to Environmental Toxicants cohort. We found non-linear associations of maternal CHO intake during pregnancy with offspring metabolic health during peripuberty. After adjusting for maternal age, and child age, sex and pubertal status, children whose mothers were in the fourth v. first quartile of total CHO intake during the third trimester had 0·42 (95 % CI -0·01, 0·08) ng/ml lower C-peptide and 0·10 (95 % CI -0·02, 0·22) units lower C-peptide insulin resistance (CP-IR). We found similar magnitude and direction of association with respect to net CHO intake during the first trimester and offspring C-peptide and CP-IR. Maternal CHO intake during pregnancy was not associated with offspring adiposity. In this study of mother-child pairs in Mexico City, children born to women in the highest quartile of CHO intake during pregnancy had lowest C-peptide and CP-IR during peripuberty. Additional research is warranted to replicate and identify mechanisms.

Risks of overweight in the offspring of women with gestational diabetes at different developmental stages: A meta-analysis with more than half a million offspring.

We conducted a meta-analysis to evaluate the association of maternal gestational diabetes mellitus (GDM) and offspring overweight from birth to adulthood, and to assess the effects of lifestyle interventions in women with GDM on this risk of offspring overweight. We identified literature from PubMed and 12 other electronic databases and retrieved relevant literature published before October 20, 2020. Random-effects model analysis was used to calculate relative risks (RRs) of overweight and weighted mean differences of body mass index among children stratified into different developmental stages. Forty-nine cohort studies (n = 559,377) and four randomized controlled trials (n = 1277) were included. We found that offspring of women with GDM were at an increased risk for overweight with age, from 1.14 (95% confidence interval [CI]: 1.06-1.22) under 5 years, 1.37 (95% CI: 1.31-1.44) at 5 to <10 years, 2.00 (95% CI: 1.79-2.23) at 10 to <18 years, to 2.05 (95% CI: 1.65-2.55) over 18 years of age (p < 0.05 for differences among groups). However, it was not observed that lifestyle interventions for GDM decreased the elevated overweight risk (RR: 0.94, 95% CI: 0.80-1.11, I2 = 0.0%). These findings highlight the need for adopting an active and healthy lifestyle in this high-risk group.

Impact of graded maternal dietary fat content on offspring susceptibility to high-fat diet in mice.

Maternal high-fat diet (HFD) increases offspring obesity, yet the impacts of different levels of maternal dietary fat have seldom been addressed. In mice, the impact of graded maternal dietary fat on offspring adiposity and offspring's later susceptibility to HFD were assessed. Lactating mice were fed diets with graded fat content from 8.3% to 66.6%. One male and one female pup from each litter were weaned onto a low-fat diet for 15 weeks. HFD (41.7%) was then introduced to half of the offspring for 12 weeks. Offspring body weight and adiposity were positively related to maternal dietary fat content and were higher when mothers were exposed to HFD. The maternal diet effect was nonlinear and sex dependent. A maternal dietary fat of 41.7% and above exaggerated the offspring body weight gain in males but was not significant in females. Maternal 8.3% fat and 25% fat diets led to the highest daily energy expenditure and respiratory exchange ratio in offspring. Offspring fed a low-fat diet had higher daily energy expenditure and respiratory exchange ratio than those fed an HFD. Increasing maternal dietary fat during lactation, and HFD in later life, had significant and interacting impacts on offspring obesity. Maternal diet had a bigger impact on male offspring. The effects of maternal dietary fat content were nonlinear.

Co-Evolution of Breast Milk Lipid Signaling and Thermogenic Adipose Tissue.

Breastfeeding is a unique and defining behavior of mammals and has a fundamental role in nourishing offspring by supplying a lipid-rich product that is utilized to generate heat and metabolic fuel. Heat generation from lipids is a feature of newborn mammals and is mediated by the uncoupling of mitochondrial respiration in specific fat depots. Breastfeeding and thermogenic adipose tissue have a shared evolutionary history: both have evolved in the course of homeothermy evolution; breastfeeding mammals are termed “thermolipials”, meaning “animals with warm fat”. Beyond its heat-producing capacity, thermogenic adipose tissue is also necessary for proper lipid metabolism and determines adiposity in offspring. Recent advances have demonstrated that lipid metabolism in infants is orchestrated by breast milk lipid signals, which establish mother-to-child signaling and control metabolic development in the infant. Breastfeeding rates are declining worldwide, and are paralleled by an alarming increase in childhood obesity, which at least in part may have its roots in the impaired metabolic control by breast milk lipid signals.