Offspring Adiposity Research Articles

Influence of Maternal Adipokines on Anthropometry, Adiposity, and Neurodevelopmental Outcomes of the Offspring.

Pregnancy is distinguished by a multitude of intricate interactions between the mother and the new individual, commencing at implantation and persisting until the maturation and integration of the fetal apparatus and systems. The physiological increase in fat mass during pregnancy and the association of maternal obesity with adverse neonatal outcomes have directed attention to the study of maternal adipokines as participants in fetal development. Interestingly, maternal concentrations of certain adipokines such as adiponectin, leptin, tumor necrosis factor-alpha, and interleukin-6 have been found to be associated with offspring anthropometry and adiposity at birth and at three months of age, even with neurodevelopmental alterations later in life. This is partly explained by the functions of these adipokines in the regulation of maternal metabolism and placental nutrient transport. This review compiles, organizes, and analyzes the most relevant studies on the association between maternal adipokines with anthropometry, adiposity, and neurodevelopmental outcomes of the offspring. Furthermore, it proposes the underlying mechanisms involved in this association.

Maternal weight status at conception predicts offspring body fat at age 11 years: population data from the Japan Kids Body Composition Study using dual-energy X-ray absorptiometry

BackgroundMaternal preconception overweight status has been reported to be associated with an increased risk of overweight offspring. However, there are no published population-based studies on the association between maternal preconception weight and offspring body fat measured by dual-energy X-ray absorptiometry (DXA). The present population-based retrospective cohort study aimed to examine the association between maternal weight at conception and offspring body fat measured by DXA.MethodsThe source population consisted of 5th-grade students (1244 students aged 11 years) registered at 8 municipal elementary schools in Kitakata, Fukuroi, Hamamatsu, and Himeji in Japan. The present analyses included 964 participants who provided complete information. Maternal body mass index (BMI) at conception was calculated using records in the Mother and Child Health Handbook (MCHH). Offspring body fat at age 11 years was measured with the same QDR-4500A DXA instrument in a mobile test room that was brought to each school. With regard to the prediction of excess fat in offspring, the area under the curve (AUC) calculated with receiver operating characteristic curve analysis was used to quantify the diagnostic accuracy of maternal BMI at conception.ResultsAdjusted odds ratios for excess body fat in offspring of the overweight mother group (odds ratios, 4.93 to 15.32) were significantly higher than those in the non-overweight mother group. For the prediction of excess offspring fat, AUCs and 95% confidence intervals for maternal BMI at conception were greater than 0.5.ConclusionMaternal overweight status at conception might be a risk factor for excess body fat in offspring. Maternal BMI values calculated using MCHH data have the potential to distinguish between the presence and absence of excess fat in the next generation.

Maternal adiposity and perinatal and offspring outcomes: an umbrella review.

Maternal adiposity deleteriously affects obstetrical health and has been associated with long-term adverse consequences in offspring. Here we conducted an umbrella review encompassing 194 observational meta-analyses, 10 Mendelian randomization studies and 748 interventional meta-analyses to appraise the published evidence on the associations between maternal adiposity and perinatal and offspring outcomes. Evidence grading suggested that 17 (8.8%) observational meta-analyses were supported by convincing evidence for 12 outcomes: maternal adiposity was associated with an increased risk of caesarean delivery following labour induction, infant mortality, Apgar score <7 at 1 min, antenatal depression, offspring overweight and obesity, early timing of puberty onset in daughters, attention deficit hyperactivity disorder, cerebral palsy, congenital heart disease and spina bifida (OR/RR ranging from 1.14 to 2.31), as well as increased offspring body fat percent and fat mass (SMD 0.31 and 0.35, respectively). Among these outcomes, interventional meta-analyses supported that maternal weight loss interventions significantly reduced the risk of antenatal depression but not low Apgar scores; these interventions also could not reduce offspring fat mass or body fat percent. Evidence from Mendelian randomization studies supported a causal relationship between maternal adiposity and gestational diabetes mellitus, preeclampsia, birth size and offspring adiposity. Our findings highlight that while observational meta-analyses reveal associations between maternal adiposity and various adverse perinatal and offspring outcomes, convincing, unbiased evidence or support from Mendelian randomization studies is limited. Maternal pre-conceptional and prenatal weight loss interventions can reduce some, but not all, of these adverse effects.

Quantifying the effect of interpregnancy maternal weight and smoking status changes on childhood overweight and obesity in a UK population-based cohort.

Maternal preconception and pregnancy exposures have been linked to offspring adiposity. We aimed to quantify the effect of changes in maternal weight and smoking status between pregnancies on childhood overweight/obesity (≥ 85th centile) and obesity (≥ 95th centile) rates in second children. Records for 5612 women were drawn from a population-based cohort of routinely collected antenatal healthcare records (2003-2014) linked to measured child body mass index (BMI) age 4-5 years. We applied the parametric G-formula to estimate the effect of hypothetical changes between pregnancy-1 and pregnancy-2 compared to the natural course scenario (without change) on child-2 BMI. Observed overweight/obesity and obesity in child-2 at age 4-5 years were 22.2% and 8·5%, respectively. We estimated that if all mothers started pregnancy-2 with BMI 18·5-24·9 kg/m² and all smokers stopped smoking, then child-2 overweight/obesity and obesity natural course estimates of 22.3% (95% CI 21.2-23.5) and 8·3% (7·6-9·1), would be reduced to 18.5% (17.4-19.9) and 6.2% (5.5-7.0), respectively. For mothers who started pregnancy-1 with BMI 18·5-24·9 kg/m², if all smokers stopped smoking, child-2 overweight/obesity and obesity natural course estimates of 17.3% (16.0-18.6) and 5·9% (5·0-6·7) would be reduced to 16.0% (14.6-17.3) and 4·9% (4·1-5·7), respectively. For mothers who started pregnancy-1 with BMI ≥30 kg/m², if BMI was 18·5-24·9 kg/m² prior to pregnancy-2, child-2 overweight/obesity and obesity natural course estimates of 38.6% (34.7-42.3) and 17·7% (15·1-20·9) would be reduced to 31.3% (23.8-40.0) and 12.5 (8.3-17.4), respectively. If BMI was 25.0-29.9 kg/m² prior to pregnancy-2, these estimates would be 34.5% (29.4-40.4) and 14.6% (11.2-17.8), respectively. Interventions supporting women to lose/maintain weight and quit smoking between pregnancies could help reduce rates of overweight/obesity and obesity in second children. The most effective interventions may vary by maternal BMI prior to the first pregnancy.

Prenatal exposure to per- and polyfluoroalkyl substances and sex-specific associations with offspring adiposity at 10 years of age: Metabolic perturbation plays a role

BackgroundPer- and polyfluoroalkyl substances (PFAS) have been suspected as potential environmental obesogens, with several mechanisms being proposed, including the role of metabolomics. However, current epidemiological studies have yielded inconclusive findings. ObjectivesWe aimed to estimate the associations of prenatal exposure to PFAS with offspring adiposity measures, and to explore the potential metabolic pathways underlying these associations. MethodsA total of 464 mother–child pairs from the Sheyang Mini Birth Cohort Study (SMBCS) were included in this study. Cord serum concentrations of 12 PFAS and urine metabolite profiles at age 10 were obtained from the SMBCS database. Adiposity-related anthropometric measurements and body composition estimates of children aged 10 were used to assess offspring obesity. Multiple linear regression models and quantile g-computation were conducted to estimate the associations of prenatal exposure to individual and multiple PFAS with obesity at 10 years old. Metabolomics analysis was performed to characterize the biological pathways associated with PFAS exposure or obesity, subsequently identifying the overlapping metabolic pathways underlying the PFAS-obesity relationship. ResultsPrenatal exposure to several PFAS was significantly associated with elevated obesity-related markers in 10-year-old children. After stratification by sex, the effects were more pronounced in girls. Quantile g-computation results indicated that exposure to higher levels of PFAS mixtures during pregnancy was associated with increased odds of obesity in girls, with PFNA emerging as the predominant driving compound. Untargeted metabolomics results showed that several amino acid metabolic pathways were characterized as the overlapping pathways underlying the above associations. ConclusionsTaken together, our findings suggested the potential obesogenic effects of prenatal exposure to PFAS and offered insight into the possible metabolic mechanisms underlying PFAS-related offspring obesity.

Gestational exposure to BPA alters the expression of glucose and lipid metabolic mediators in the placenta: Role in programming offspring for obesity

Bisphenol A (BPA) exposure during pregnancy is known to predispose offspring to obesity in later life. Our previous studies demonstrated obesogenic effects in BPA-exposed offspring, including excess body fat, increased feed efficiency, adipocyte hypertrophy, and altered leptin signaling. However, the role of the placenta in mediating these effects remained unclear. This study investigates the mechanisms by which BPA exposure affects placental glucose and lipid transporters and their impact on offspring adiposity in Wistar rats. Dams were orally gavaged with BPA [0.4 (low dose-LD) and 4.0 (high dose-HD) μg/kg body weight] from gestational day (gD) 4–14. Gestational exposure to LD BPA increased the expression of 11β hydroxysteroid dehydrogenase 1 (11β HSD1) and estrogen receptor alpha (ERα) proteins (p<0.05) in the placenta compared to control and HD BPA. Similar changes were observed in the expression of mTOR signaling mediators, fatty acid transporters, and intracellular fatty acid-binding proteins. There were no changes in the dam's body weight or lipid and glucose profiles. However, there was a dose dependent increase in glucose transporter (GLUT1) expression in the placenta. While LD BPA increased hexokinase 2 expression in the placenta, HD BPA had no effect. Both doses of BPA increased IL6 expression, but only LD BPA exposure increased PPAR-gamma expression. Additionally, BPA exposure induced ADRP expression and localization, suggesting potential lipid overload in the placenta. Furthermore, BPA exposure altered the placental epigenetic profile, with increased expression of DNA methyltransferases (DNMTs). Overall, gestational BPA exposure led to dose-specific alterations in placental glucose and lipid metabolic activities, possibly playing an role in increasing the supply of these macronutrients to the fetus and predisposing the offspring to obesity.

Protective Eating Behaviors Among Children at Higher Risk for Obesity in the INSIGHT Study.

Background: Maternal pre-pregnancy body mass index (BMI) is positively associated with offspring overweight. We investigated behaviors that may confer resilience to childhood overweight development by examining appetitive traits in at-risk children born to mothers with pre-pregnancy overweight. Methods: This secondary analysis included children born to mothers with pre-pregnancy BMI ≥25 kg/m2 from the Intervention Nurses Start Infants Growing on Health Trajectories Study (N = 84). Mothers completed the Child Eating Behavior Questionnaire (CEBQ) at child ages 30 months and 6 years. t-tests assessed differences in appetitive traits (CEBQ subscale scores) between children with overweight (BMI ≥85th percentile) and without overweight (BMI <85th percentile). Results: The 87 children (41 female [47%]) included in this analysis were predominantly White and non-Hispanic (93%), and 34 (39%) had overweight at age 6 years. Compared with children with overweight, children without overweight had mothers who reported greater child slowness in eating when their child was 30 months (p = 0.04) and 6 years old (p = 0.004). Similarly, mothers of children without overweight reported higher child satiety responsiveness, lower enjoyment of food, and lower food responsiveness (p < 0.001 for all) when their child was 6 years old. Conclusion: Eating slower, higher satiety responsiveness, lower enjoyment of food, and lower food responsiveness were protective factors against developing overweight among those with familial risk. Strategies to promote the development of slower eating and satiety responsiveness could be explored as part of obesity prevention strategies.

Differentially methylated regions interrogated for metastable epialleles associate with offspring adiposity.

Aim: Assess if cord blood differentially methylated regions (DMRs) representing human metastable epialleles (MEs) associate with offspring adiposity in 588 maternal-infant dyads from the Colorado Health Start Study.Materials & methods: DNA methylation was assessed via the Illumina 450K array (~439,500 CpG sites). Offspring adiposity was obtained via air displacement plethysmography. Linear regression modeled the association of DMRs potentially representing MEs with adiposity.Results & conclusion: We identified two potential MEs, ZFP57, which associated with infant adiposity change and B4GALNT4, which associated with infancy and childhood adiposity change. Nine DMRs annotating to genes that annotated to MEs associated with change in offspring adiposity (false discovery rate<0.05). Methylation of approximately 80% of DMRs identified associated with decreased change in adiposity.

24 - Exploring the impact of maternal weight loss on metabolic function in offspring adipose tissue

24 - Exploring the impact of maternal weight loss on metabolic function in offspring adipose tissue

Why do preconception and pregnancy lifestyle interventions demonstrate limited success in preventing overweight and obesity in children? A scoping review investigating intervention complexity, process evaluation components, and author interpretations.

Preventing childhood obesity from early life is considered essential. However, evidence from recent systematic reviews has highlighted inconsistent results and limited effectiveness of preconception and pregnancy lifestyle interventions regarding offspring weight outcomes and adiposity. Therefore, to improve our understanding regarding the mixed success of these early life interventions, we conducted a scoping review examining intervention complexity, process evaluation components, and authors' statements. Eligible articles (preconception or pregnancy lifestyle trials with offspring data beyond 1month of age) were identified by searching databases (PubMed, Embase, and CENTRAL), previous reviews, and performing CLUSTER searches. The Intervention Complexity Assessment Tool for Systematic Reviews (iCAT_SR) was used to evaluate intervention complexity. A thematic analysis provided insight into process evaluation components and authors' interpretations. Finally, an expert consultation on the results was conducted. We identified 40 eligible publications corresponding to 27 trials. Only two trials started before conception. Potential reasons for interventions' limited success included the late intervention initiation, short intervention duration, and insufficient sample size. Few studies reported process evaluations and included stakeholder involvement, which are essential according to the expert group. We discuss current limitations and outline suggestions for future interventions in this field of research.

Nutritional counselling and risk factors for obesity: an observational study in toddlers

BackgroundNutrition exerts a fundamental role in the prevention of obesity (OB). The aim of this study was to assess the extent to which well recognized risk factors for early OB can be associated to overweight (OW) or OB under a standardized nutritional approach and surveillance in toddlers.MethodsThe eligible population was represented by 676 toddlers aged 24–36 months, assigned to 18 primary care pediatricians trained on nutritional issues who shared a standardized nutritional approach. Six-hundred-twenty-nine children (333 boys), mean age 27.8 ± 4.2 months were effectively included in this observational study. Parents received nutritional advice with particular emphasis to proteins and sugar composition supported by leaflets and reinforced at each visit. Body mass index was assessed at the age of 24–36 months. The following individual and family risk factors were considered: gestational age, birth weight, eutocic/caesarean delivery, milk feeding history, household smoking or antibiotics exposure, parents’ weight, height and educational level. Prevalence of OW/OB was compared to a group of 742 toddlers (373 boys) under usual care.ResultsUnder a standardized nutritional counselling, 28.1% toddlers were classified as OW/OB compared to 36.9% toddlers under usual care (p = 0.005). In unadjusted models, parental OW/OB was significantly associated to OW/OB in toddlers (p < 0.01), while high birth weight did not reach statistical significance (p = 0.07). In adjusted models, including all the explanatory variables studied, only paternal OW/OB vs. normal weight was significantly associated to OW/OB in toddlers (OR 2.035, 95% confidence interval 1.206–3.436). No protective effect of exclusive breast feeding during the first 6 months of age was demonstrated.ConclusionsToddlers under a standardized nutrition counselling focused to limit protein and simple sugars, showed lower prevalence of OW/OB compared to usual care. Healthy promotion activities should take into account the influence of paternal BMI on the offspring adiposity.

Metformin exposure during pregnancy and lactation affects offspring's long-term body weight and adipose tissue mass independent of the maternal metabolic state

The increasing prevalence of obesity, type 2 diabetes mellitus (T2DM), and gestational diabetes (GDM) among pregnant women has risen dramatically worldwide. The antihyperglycemic drug metformin is the most common drug for T2DM treatment in non-pregnant individuals; nevertheless, it is increasingly being used for diabetes-complicated pregnancies. Studies on the long-term metabolic effects of this drug in offspring remain scarce. This work aimed to determine the effect of metformin exposure during pregnancy and lactation on the offspring of a model of diet-induced maternal hyperglycemia.Cohorts of pregnant mice were fed a 46% fat diet (HFD) or a control standard diet (SD). A group of dams were exposed to metformin during pregnancy and lactation. After weaning, the offspring were fed SD for 8 weeks and then challenged with a 46% HFD after puberty for 12 weeks. Irrespective of the maternal diet, offspring of metformin-exposed mothers had a lower body weight and reduced inguinal white adipose tissue (iWAT) mass after HFD challenge. This was associated with increased expression of Pparg, Fabp4, Glut4, Srebp1, and Fasn in the iWAT during adulthood in the metabolically impaired dams exposed to metformin, suggesting increased adipogenesis and de novo lipogenesis. Increased expression of Fasn associated with decreased methylation levels at its promoter and proximal coding region in the iWAT was found. These results suggest that metformin modulates gene expression levels by epigenetic mechanisms in maternal metabolic-impaired conditions.

Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers During Childhood and Adolescence

To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. Project Viva is a prospective prebirth cohort (n=2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n=1107), early adolescence (n=1027), and mid-adolescence (n=693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI). In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n=27) had a higher BMI z-score (β; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI. Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

The Effect of Prenatal Docosahexaenoic Acid Supplementation on Offspring Fat Mass and Distribution at 24 Months Old

BackgroundExcessive gestational weight gain (GWG) is related to increased offspring fat accrual, and increased fat mass (FM) is related to obesity development. Prenatal DHA supplementation has been linked to lower levels of offspring FM; however, conflicting data exist. ObjectivesThis study aimed to determine if there is a protective effect of prenatal DHA supplementation on offspring fat accrual and adipose tissue deposition at 24 mo in offspring born to females who gain excessive weight compared with nonexcessive weight during pregnancy. We also explored if the effect of DHA dose on FM differed by offspring sex. MethodsInfants born to females who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE) were recruited. In ADORE, females were randomly assigned to either a high or low prenatal DHA supplement. Offspring body composition and adipose tissue distribution were measured using dual-energy x-ray absorptiometry (DXA). GWG was categorized as excessive or not excessive based on clinical guidelines. ResultsFor total FM, there was a significant main effect for the DHA dose (P = 0.03); however, the dose by GWG status was nonsignificant (P = 0.44). Therefore, a higher prenatal DHA dose was related to greater offspring FM (622.9 g greater) and unrelated to GWG status. When investigating a DHA dose by sex effect, a significant main effect for DHA dose (P = 0.01) was detected for central FM. However, no interaction was detected (P = 0.98), meaning that both boys and girls had greater central FM if their mother was assigned to the higher DHA dose. ConclusionsGreater prenatal DHA supplementation was associated with greater offspring FM and adipose tissue distribution at 24 mo. It will be important to understand if these effects persist into childhood.This trial was registered at clinicaltrials.gov as NCT03310983.

Impact of an active lifestyle on cardiovascular autonomic modulation and oxidative stress in males with overweight and parental history of hypertension.

Family history of hypertension is associated with early autonomic dysfunction and increased oxidative stress. These alterations have been found to be reinforced by the overweight factor. Conversely, an active lifestyle is effective in improving the mechanisms regulating blood pressure control. Hence, we ought to investigate the effects of an active lifestyle on the hemodynamic, autonomic and oxidative stress parameters in individuals carrying both family history of hypertension and overweight risk factors. Fifty-six normotensive males were divided into four groups: eutrophic offspring of normotensive parents (EN, n = 12), eutrophic and inactive with hypertensive parents (EH, n = 14), overweight and inactive with hypertensive parents (OH, n = 13), and overweight and physically active with hypertensive parents (OAH, n = 17). Cardiovascular autonomic modulation was assessed by heart rate (HRV) and blood pressure (BPV) variability indexes. Oxidative stress included pro/antioxidant markers and nitrite concentration. Inactive offspring of hypertensive parents (EH and OH) showed higher LFSBP (vs EN), an indicator of sympathetic outflow to the vasculature and reduced anti-oxidant activity (vs EN), while higher pro-oxidant markers were found exclusively in OH (vs EN and EH). Conversely, the OAH group showed bradycardia, higher vagally-mediated HFabs index (vs OH and EN), lower sympathovagal balance (vs OH) and preserved LFSBP. Yet, the OAH showed preserved pro/antioxidant markers and nitrite levels. Our findings indicates that overweight offspring of hypertensive parents with an active lifestyle have improved hemodynamic, cardiac autonomic modulation and oxidative stress parameters compared to their inactive peers.

The association of maternal gestational weight gain with cardiometabolic risk factors in offspring: a systematic review and meta-analysis.

Gestational weight gain (GWG) is known to be a risk factor for offspring obesity, a precursor of cardiometabolic diseases. Accumulating studies have investigated the association of GWG with offspring cardiometabolic risk factors (CRFs), leading to inconsistent results. This study synthesized available data from cohort studies to examine the effects of GWG on offspring CRFs. Four electronic databases, including PubMed, Web of Science, Scopus, and Embase, were searched through May 2023. Cohort studies evaluating the association between GWG and CRFs (fat mass [FM], body fat percentage [BF%], waist circumference [WC], systolic blood pressure [SBP] and diastolic blood pressure, high-density-lipoprotein cholesterol [HDL-C] and low-density-lipoprotein cholesterol, triglyceride [TG], total cholesterol, fasting blood glucose, and fasting insulin levels) were included. Regression coefficients, means or mean differences with 95% confidence intervals [CIs], or standard deviations were extracted. Thirty-three cohort studies were included in the meta-analysis. Higher GWG (per increase of 1 kg) was associated with greater offspring FM (0.041 kg; 95% CI, 0.016 to 0.067), BF% (0.145%; 95% CI, 0.116 to 0.174), WC (0.154 cm; 95% CI, 0.036 to 0.272), SBP (0.040 mmHg; 95% CI, 0.010 to 0.070), and TG (0.004 mmol/L; 95% CI, 0.001 to 0.007), and with lower HDL-C (-0.002 mmol/L; 95% CI, -0.004 to 0.000). Consistently, excessive GWG was associated with higher offspring FM, BF%, WC, and insulin, and inadequate GWG was associated with lower BF%, low-density lipoprotein cholesterol, total cholesterol, and TG, compared with adequate GWG. Most associations went non-significant or attenuated with adjustment for offspring body mass index or FM. Higher maternal GWG is associated with increased offspring adiposity, SBP, TG, and insulin and decreased HDL-C in offspring, warranting a need to control GWG and to screen for cardiometabolic abnormalities of offspring born to mothers with excessive GWG. PROSPERO registration no. CRD42023412098.

Abstract P409: Maternal Macronutrient Intake at Pregnancy and Offspring Growth Trajectory Before Adulthood: A Prospective Analysis in the Growing Up Today Study 2 Cohort

Background: Childhood obesity has become a public health challenge globally, with increasing prevalence worldwide. Existing studies have indicated a potential link between maternal macronutrients intake and subsequent weight changes in their offspring during childhood. However, the long-term relationship between maternal macronutrient consumption at pregnancy and the growth trajectory of offspring into adulthood remains unclear. Objectives: We aim to investigate the relationship between maternal macronutrients intake at pregnancy and the trajectory of the offspring BMI z-score, as well as the risk of becoming overweight or obese before adulthood. Method: We included 5,700 children from the Growing Up Today Study 2 born to 4,697 mothers who participated in the Nurses’ Health Study II . Diet was assessed using a validated food frequency questionnaire in 1991 approximately during or before the pregnancy at issue. Age- and gender-specific BMI thresholds described by the International Obesity Task Force were used to define overweight and obesity in childhood and adolescence. Multivariable linear and log-binomial regression models with generalized estimating equations were used to evaluate the association between maternal macronutrients intake at pregnancy and offspring BMI z-score trajectory and the risk of overweight or obesity. Results: During follow-up, 2145 (37.6%) GUTS2 participants met the criteria of overweight or obesity.After multivariate adjustment for maternal, offspring risk factors, total maternal total energy and carbohydrate percent energy, comparing to the 1 st quartile, the highest quartile of total protein consumption at pregnancy was associated with 0.14-unit [β: 0.14 (95% CI: 0.02, 0.26; P-trend = 0.03)] increase in BMI z-score, while no significant association was observed for the risk of offspring overweight or obesity [RR: 1.17 (95% CI: 0.94, 1.46; P-trend = 0.12)]. The relationship persisted for the top quartile of animal protein energy intake [β: 0.14 (95% CI: 0.01, 0.27; P-trend = 0.03)], but not for vegetable protein consumption. Intakes of dietary fats and carbohydrates were not associated with BMI z-score or risk of overweight or obesity. Furthermore, individual macronutrient subgroups, such as saturated fats, mono- and poly-unsaturated fats, or whole grains and refined grains, were not associated with the outcomes of interest, either. Conclusion: Maternal animal protein intake at pregnancy is positively associated with higher offspring BMI z-score before adulthood, but not the risk of developing overweight or obesity during childhood. Other macronutrients are not significantly associated with these childhood body weight outcomes. Overall, these data suggest that the macronutrient composition of maternal diet at peri-pregnancy period has minimal impact on offspring body weight in this well-nourished population.

Associations between a paternal healthy lifestyle score and its individual components with childhood overweight and obesity.

Maternal healthy lifestyle behaviors during pregnancy have been associated with reduced risk of offspring overweight and obesity (OWOB). However, there has been little investigation, in the context of the Paternal Origins of Health and Disease (POHaD) paradigm, of the potential influence of the paternal lifestyle on offspring OWOB. To describe paternal healthy lifestyle factors around pregnancy and investigate their associations, individually and combined, with offspring risk of OWOB during childhood. Participants included 295 father-child pairs from the Lifeways Cross-Generation Cohort Study. A composite paternal healthy lifestyle score (HLS) based on having a high dietary quality (top 40% of the Healthy Eating Index-2015), meeting physical activity guidelines (≥450 MET-min/week of moderate-to-vigorous physical activity), having a healthy body mass index (BMI) (18.5-24.9kg/m2 ), being a non-smoker, and having no/moderate alcohol intake, was calculated (range 0-5). Paternal HLS (and individual components) associations with child BMI and waist-to-height ratio (WHtR) at age 5 and 9 years were assessed using linear (BMI z-scores and WHtR) and logistic (IOTF categories) regression analyses, adjusted for sociodemographic characteristics. At age 5 and 9 years, 23.5% and 16.9% of children were classified as living with OWOB, respectively. Of the 160 pairs with a complete HLS, 45.0% of the fathers had unfavorable lifestyle factors, determined by a low HLS between 0 and 2 points. Although a low paternal HLS was not significantly associated with a higher risk of childhood OWOB measured using either BMI z-scores and IOTF categories, it was associated with a greater child WHtR, an indicator of central adiposity, at 9 years of age (β [95% CI]=0.04 [0.01,0.07]). Almost half of the fathers had unfavorable lifestyle factors around pregnancy. A low paternal HLS was associated with a greater child WHtR at 9 years but not with a higher risk of childhood OWOB when measured by BMI z-scores or IOTF categories.

Maternal gestational hypertension, smoking and pre-eclampsia are associated with metabolic dysfunction-associated fatty liver disease in overweight offspring.

Due to a steep increase in obesity, metabolic dysfunction-associated fatty liver disease (MAFLD) has also become the most common chronic hepatic condition among children and adolescents. Various maternal and pregnancy-related factors have also been implicated in the development of MAFLD, but human studies remain scarce. Comprehensive data of 460 overweight or obese children aged 2-16 years were collected and combined with data on selected maternal and pregnancy-related factors for a case-control study. MALFD was defined as alanine aminotransferase >2× upper limit of normal. Children with and without MAFLD were compared regarding to the study variables and multivariable regression analysis was utilized. Median age of the study children was 11.8 (quartiles 9.1-14.2) years; 44% were girls and 17.8% had MAFLD. Children with MAFLD were older (12.7 vs. 11.6 years, p = 0.002), while the groups did not differ age-standardized body mass index (BMI-SDS) or gender. Factors associated with MAFLD in a multivariable model considering also the offspring's present BMI-SDS, sex, and maternal prepregnancy overweight, were child's older age (odds ratio [OR] 1.16, 95% confidence interval [CI]: 1.06-1.28), maternal gestational smoking (OR 2.01, 95% CI: 1.16-3.47), gestational hypertension (OR 3.44, 95% CI: 1.08-11.0) and pre-eclampsia (OR 2.93, 95% CI: 1.15-7.45). There was no significant association between MAFLD and maternal BMI, birth anthropometrics or perinatal complications. Maternal smoking, gestational hypertension and pre-eclampsia were associated with MAFLD among overweight or obese children. Further prospective studies are needed to verify causal relationships.

Gestational Caloric Restriction Alters Adipose Tissue Methylome and Offspring's Metabolic Profile in a Swine Model.

Limited nutrient supply to the fetus results in physiologic and metabolic adaptations that have unfavorable consequences in the offspring. In a swine animal model, we aimed to study the effects of gestational caloric restriction and early postnatal metformin administration on offspring's adipose tissue epigenetics and their association with morphometric and metabolic variables. Sows were either underfed (30% restriction of total food) or kept under standard diet during gestation, and piglets were randomly assigned at birth to receive metformin (n = 16 per group) or vehicle treatment (n = 16 per group) throughout lactation. DNA methylation and gene expression were assessed in the retroperitoneal adipose tissue of piglets at weaning. Results showed that gestational caloric restriction had a negative effect on the metabolic profile of the piglets, increased the expression of inflammatory markers in the adipose tissue, and changed the methylation of several genes related to metabolism. Metformin treatment resulted in positive changes in the adipocyte morphology and regulated the methylation of several genes related to atherosclerosis, insulin, and fatty acids signaling pathways. The methylation and gene expression of the differentially methylated FASN, SLC5A10, COL5A1, and PRKCZ genes in adipose tissue associated with the metabolic profile in the piglets born to underfed sows. In conclusion, our swine model showed that caloric restriction during pregnancy was associated with impaired inflammatory and DNA methylation markers in the offspring's adipose tissue that could predispose the offspring to later metabolic abnormalities. Early metformin administration could modulate the size of adipocytes and the DNA methylation changes.