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JAMA Network Open Jun 2024Studies on the familial effects of body mass index (BMI) status have yielded a wide range of data on its heritability.
IMPORTANCE
Studies on the familial effects of body mass index (BMI) status have yielded a wide range of data on its heritability.
OBJECTIVE
To assess the heritability of obesity by measuring the association between the BMIs of fathers, mothers, and their offspring at the same age.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from population-wide mandatory medical screening before compulsory military service in Israel. The study included participants examined between January 1, 1986, and December 31, 2018, whose both parents had their BMI measurement taken at their own prerecruitment evaluation in the past. Data analysis was performed from May to December 2023.
MAIN OUTCOMES AND MEASURES
Spearman correlation coefficients were calculated for offsprings' BMI and their mothers', fathers', and midparental BMI percentile (the mean of the mothers' and fathers' BMI cohort- and sex-specific BMI percentile) to estimate heritability. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% CIs of obesity compared with healthy BMI, according to parental BMI status.
RESULTS
A total of 447 883 offspring (235 105 male [52.5%]; mean [SD] age, 17.09 [0.34] years) with both parents enrolled and measured for BMI at 17 years of age were enrolled in the study, yielding a total study population of 1 343 649 individuals. Overall, the correlation between midparental BMI percentile at 17 years of age and the offspring's BMI at 17 years of age was moderate (ρ = 0.386). Among female offspring, maternal-offspring BMI correlation (ρ = 0.329) was somewhat higher than the paternal-offspring BMI correlation (ρ = 0.266). Among trios in which both parents had a healthy BMI, the prevalence of overweight or obesity in offspring was 15.4%; this proportion increased to 76.6% when both parents had obesity and decreased to 3.3% when both parents had severe underweight. Compared with healthy weight, maternal (OR, 4.96; 95% CI, 4.63-5.32), paternal (OR, 4.48; 95% CI, 4.26-4.72), and parental (OR, 6.44; 95% CI, 6.22-6.67) obesity (midparent BMI in the ≥95th percentile) at 17 years of age were associated with increased odds of obesity among offspring.
CONCLUSIONS AND RELEVANCE
In this cohort study of military enrollees whose parents also underwent prerecruitment evaluations, the observed correlation between midparental and offspring BMI, coupled with a calculated narrow-sense heritability of 39%, suggested a substantive contribution of genetic factors to BMI variation at 17 years of age.
Topics: Humans; Body Mass Index; Male; Female; Israel; Adolescent; Obesity; Cohort Studies; Adult; Fathers
PubMed: 38941093
DOI: 10.1001/jamanetworkopen.2024.19029 -
International Journal of Obesity (2005) Jun 2024Intrauterine metabolic reprogramming occurs in mothers with obesity during gestation, putting the offspring at high risk of developing obesity and associated metabolic...
BACKGROUND/OBJECTIVES
Intrauterine metabolic reprogramming occurs in mothers with obesity during gestation, putting the offspring at high risk of developing obesity and associated metabolic disorders even before birth. We have generated a mouse model of maternal high-fat diet-induced obesity that recapitulates the metabolic changes seen in humans born to women with obesity.
METHODS
Here, we profiled and compared the metabolic characteristics of bone marrow cells of newly weaned 3-week-old offspring of dams fed either a high-fat (Off-HFD) or a regular diet (Off-RD). We utilized a state-of-the-art flow cytometry, and targeted metabolomics approach coupled with a Seahorse metabolic analyzer.
RESULTS
We revealed significant metabolic perturbation in the offspring of HFD-fed vs. RD-fed dams, including utilization of glucose primarily via oxidative phosphorylation. We also show a reduction in levels of amino acids, a phenomenon previously linked to bone marrow aging. Using flow cytometry, we found changes in the immune complexity of bone marrow cells and identified a unique B cell population expressing CD19 and CD11b in the bone marrow of three-week-old offspring of high-fat diet-fed mothers. Our data also revealed increased expression of Cyclooxygenase-2 (COX-2) on myeloid CD11b, and on CD11b B cells.
CONCLUSIONS
Altogether, we demonstrate that the offspring of mothers with obesity show metabolic and immune changes in the bone marrow at a very young age and prior to any symptomatic metabolic disease.
PubMed: 38937647
DOI: 10.1038/s41366-024-01563-x -
The Journal of Nutrition Jun 2024The American Academy of Pediatrics recommends juice introduction after 12 months of age. Juice consumption has been linked to childhood obesity and cardiometabolic risk....
BACKGROUND
The American Academy of Pediatrics recommends juice introduction after 12 months of age. Juice consumption has been linked to childhood obesity and cardiometabolic risk. We examined the prospective relationship between the age of juice introduction and primary and secondary cardiometabolic outcomes in middle childhood.
METHODS
Parents reported the age of juice introduction on Upstate KIDS questionnaires completed between 4-18 months of age. The quantity and type of juice introduced was not measured. Anthropometry, blood pressure (BP), and arterial stiffness by pulse wave velocity (PWV) were measured for 524 children at study visits between 8-10 years old (2017-2019). Age- and sex-adjusted z-scores were calculated for anthropometrics using the Centers for Disease Control and Prevention reference. Plasma lipids, hemoglobin A1c (HbA1c), and C-reactive protein (CRP) in a subset of children were also measured (n=248). Associations between age at juice introduction (categorized as <6, 6 to <12, ≥ 12 months) and outcomes were estimated using mean differences and odds ratios, applying generalized estimating equations to account for correlations between twins.
RESULTS
Approximately 18% of children were introduced to juice at < 6 months old, 52% between 6 to <12 months, and 30% ≥ 12 months of age. Children who were introduced to juice prior to 6 months had higher systolic BP (3.13 mmHg; 95% confidence interval 0.52, 5.74), heart rate (4.46 bpm; 1.05, 7.87), and mean arterial pressure (2.08 mmHg; 0.15, 4.00) compared to those introduced ≥ 12 months after covariate adjustment including sociodemographic factors and maternal pre-pregnancy body mass index. No adjusted differences in anthropometry, lipids, HbA1c, and CRP levels were found.
CONCLUSION
Early juice introduction during infancy was associated with higher systolic BP, heart rate, and mean arterial pressure in middle childhood.
CLINICAL TRIAL REGISTRY
This trial was registered at clinicaltrials.gov as NCT03106493 (https://clinicaltrials.gov/study/NCT03106493?term=upstate%20KIDS&rank=1).
PubMed: 38936550
DOI: 10.1016/j.tjnut.2024.06.014 -
PloS One 2024Diet-induced obesity reduces oocyte quality mainly by impacting oocyte mitochondrial functions. Moreover, maternal obesity is associated with mitochondrial dysfunction...
Diet-induced obesity reduces oocyte quality mainly by impacting oocyte mitochondrial functions. Moreover, maternal obesity is associated with mitochondrial dysfunction in oocytes of their adult offspring. However, these effects were reported only in fully grown oocytes, mainly in the form of abnormal mitochondrial ultrastructure. It is unknown if obesogenic (OB) diets or maternal obesity already impact the primordial and preantral follicles. Considering the long duration and dynamics of folliculogenesis, determining the stage at which oocytes are affected and the extent of the damage is crucial for optimal reproductive management of obese patients and their daughters. Potential interaction between maternal and offspring diet effects are also not described, yet pivotal in our contemporary society. Therefore, here we examined the impact of OB diets on oocyte mitochondrial ultrastructure in primordial and activated preantral follicles in offspring from diet-induced obese or lean mothers. We used an outbred Swiss mouse model to increase the pathophysiological relevance to humans. Female mice were fed control or OB diets for 7 weeks, then mated with control males. Their female offspring were fed control or OB diets after weaning for 7 weeks (2-by-2 factorial design). Adult offspring ovarian sections were examined using transmission electron microscopy. We characterised and classified unique features of oocyte mitochondrial ultrastructure in the preantral follicles. An increase in mitochondrial matrix density was the most predominant change during follicle activation in secondary follicles, a feature that is linked with a higher mitochondrial activity. Maternal obesity increased mitochondrial density already in the primordial follicles suggesting an earlier increase in bioenergetic capacity. Maternal obesity did not induce abberant ultrastructure (abnormalities and defects) in primordial or preantral follicles. In contrast, offspring OB diet increased mitochondrial abnormalities in the primordial follicles. Further investigation of the consequences of these changes on oocyte metabolic regulation and stress levels during folliculogenesis is needed.
Topics: Animals; Oocytes; Female; Ovarian Follicle; Mice; Mitochondria; Pregnancy; Obesity; Male; Obesity, Maternal; Prenatal Exposure Delayed Effects; Diet, High-Fat
PubMed: 38935642
DOI: 10.1371/journal.pone.0305912 -
JAMA Jun 2024In 2016, our institution adopted a pregnancy-related venous thromboembolism (VTE) prophylaxis protocol based on American College of Obstetricians and Gynecologists...
IMPORTANCE
In 2016, our institution adopted a pregnancy-related venous thromboembolism (VTE) prophylaxis protocol based on American College of Obstetricians and Gynecologists guidelines that recommended postpartum heparin-based chemoprophylaxis (enoxaparin) based on a risk-stratified algorithm. In response to increased wound hematomas without significant reduction in VTE using this protocol, a more selective risk-stratified approach was adopted in 2021.
OBJECTIVE
To evaluate outcomes of the more selective risk-stratified approach to heparin-based obstetric thromboprophylaxis (enoxaparin) protocol.
DESIGN, SETTING, AND PARTICIPANTS
Retrospective observational study of 17 489 patients who delivered at a single tertiary care center in the southeast US between January 1, 2016, and December 31, 2018 (original protocol), and between December 1, 2021, and May 31, 2023 (more selective protocol). Patients receiving outpatient anticoagulation for active VTE or high VTE risk during pregnancy were excluded.
EXPOSURE
Standard risk-stratified and more selective postpartum VTE chemoprophylaxis protocols.
MAIN OUTCOMES AND MEASURES
The primary outcome was clinical diagnosis of wound hematoma up to 6 weeks pos tpartum. The secondary outcome was new diagnosis of VTE up to 6 weeks post partum. We compared baseline characteristics and outcomes between groups and estimated adjusted odds ratios with 95% CIs of primary and secondary outcomes using the original protocol group as reference.
RESULTS
Of 17 489 patients included in the analysis, 12 430 (71%) were in the original protocol group and 5029 (29%) were in the more selective group. Rates of chemoprophylaxis decreased from 16% (original protocol) to 8% (more selective protocol). Patients in the more selective group were more likely to be older, be married, and have obesity or other comorbidities (hypertension, diabetes, cardiac disease). Compared with the original protocol, the more selective protocol was associated with a decrease in any wound hematoma (0.7% vs 0.3%; adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.67), specifically due to a lower rate of superficial wound hematomas (0.6% vs 0.3%; aOR, 0.43; 95% CI, 0.24-0.75). There was no significant increase in VTE or individual types of VTE (0.1% vs 0.1%; aOR, 0.40; 95% CI, 0.12-1.36).
CONCLUSIONS AND RELEVANCE
A more selective risk-stratified approach to an enoxaparin thromboprophylaxis protocol for VTE was associated with decreased rates of wound hematomas without increased rates of postpartum VTE.
PubMed: 38935391
DOI: 10.1001/jama.2024.8684 -
AJPM Focus Aug 2024Pregnancy complications, including high maternal BMI, are associated with altered early development and child health outcomes. A growing body of work links the prenatal... (Review)
Review
INTRODUCTION
Pregnancy complications, including high maternal BMI, are associated with altered early development and child health outcomes. A growing body of work links the prenatal environment, specifically maternal BMI, with respiratory infections in offspring. In this rapid review, the authors review the literature supporting the hypothesis that high maternal BMI during pregnancy is associated with childhood respiratory infection incidence.
METHODS
The authors employed systematic search criteria in known databases-EMBASE, EMCARE, MEDLINE, CINAHL, and PsychINFO-searching from inception to January 2023. Included were primary research studies that involved (1) human pregnancy, (2) pregravid or gestational overweight or obesity, and (3) childhood respiratory infection with or without hospitalization.
RESULTS
Only 7 population-based cohort studies met the criteria, investigating maternal BMI as an exposure and childhood respiratory infection as an outcome (age 6 months to 18 years). Therefore, the authors conducted a qualitative analysis, and outcomes were reported. The authors found that >85% of the albeit few published studies support the hypothesis that maternal BMI may have independent and profound consequences on respiratory infection risk across childhood.
DISCUSSION
This area of research needs large-scale, well-controlled studies to better understand the relationship between maternal BMI and childhood respiratory infection. Possible resources such as cohort catalogs and combined databases are discussed. These findings add to the growing evidence that early environmental factors influence lifelong respiratory health. By incorporating a life course approach to infectious disease risk, policy makers can put this research to work and target health vulnerabilities before they arise.
PubMed: 38933528
DOI: 10.1016/j.focus.2024.100234 -
Journal of Diabetes and Metabolic... Jun 2024Obesity and metabolic syndrome are global health concerns associated with development of different types of diseases and serious health threats in the long term. Their... (Review)
Review
BACKGROUND
Obesity and metabolic syndrome are global health concerns associated with development of different types of diseases and serious health threats in the long term. Their metabolic imbalance can be attributable to inherited and environmental factors. As a considerable environmental agent, heavy metals exposure can predispose individuals to diseases like obesity. This systematic review and meta-analysis aimed to evaluate the association between heavy metals exposure and the risk of obesity.
METHODS
PubMed/MEDLINE, EMBASE and Web of Science were systematically searched until December 17, 2022. Only observational studies that evaluated heavy metals exposure and obesity were included. Studies were excluded if they assessed maternal or prenatal exposure, the mixture of heavy metals and other chemicals, reported the association with overweight or other diseases, and undesirable study designs. The Joanna Briggs Institute checklist was used for quality assessment. The pooled adjusted odds ratio (aOR) and the pooled standardized mean difference (SMD) with their 95% confidence intervals (CIs) were calculated, respectively. The publication bias was evaluated using Egger's and Begg's tests.
RESULTS
Twenty studies (n = 127755), four case-control and sixteen analytical cross-sectional studies, were included. Lead exposure was significantly associated with a lower risk of obesity (aOR: 0.705, 95% CI: 0.498-0.997), while mercury (aOR: 1.458, 95% CI: 1.048-2.031) and barium (aOR: 1.439, 95% CI: 1.142-1.813) exposure increased the risk of obesity. No significant publication bias was found and the studies had a low risk of bias.
CONCLUSION
Overall, lead exposure reduced obesity risk, while mercury and barium exposure raised it. Further large-scale observational studies are recommended to determine the roles of heavy metals in obesity.Study registration ID: CRD42023394865.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-023-01307-0.
PubMed: 38932800
DOI: 10.1007/s40200-023-01307-0 -
Nutrients Jun 2024Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as...
Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as the optimal source of nutrition for infant growth and immune maturation, and its composition can be modulated by the maternal diet. In the present work, we investigated whether oral supplementation with and short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) to rat dams during gestation and lactation has an impact on the immune system and microbiota composition of the offspring at day 21 of life. On that day, blood, adipose tissue, small intestine (SI), mesenteric lymph nodes (MLN), salivary gland (SG), cecum, and spleen were collected. Synbiotic supplementation did not affect the overall body or organ growth of the pups. The gene expression of , , , and were upregulated in the SI, and the increase in IgA gene expression was further confirmed at the protein level in the gut wash. Synbiotic supplementation also positively impacted the microbiota composition in both the small and large intestines, resulting in higher proportions of genus, among others. In addition, there was an increase in butanoic, isobutanoic, and acetic acid concentrations in the cecum but a reduction in the small intestine. At the systemic level, synbiotic supplementation resulted in higher levels of immunoglobulin IgG2c in plasma, SG, and MLN, but it did not modify the main lymphocyte subsets in the spleen and MLN. Overall, synbiotic maternal supplementation is able to positively influence the immune system development and microbiota of the suckling offspring, particularly at the gastrointestinal level.
Topics: Animals; Gastrointestinal Microbiome; Synbiotics; Female; Bifidobacterium breve; Pregnancy; Oligosaccharides; Rats; Animals, Suckling; Dietary Supplements; Maternal Nutritional Physiological Phenomena; Lactation; Immune System; Male; Animals, Newborn
PubMed: 38931246
DOI: 10.3390/nu16121890 -
Nutrients Jun 2024The maternal microbiome plays a vital role in shaping pregnancy outcomes, but there remains a substantial gap in understanding its precise relationships to maternal... (Observational Study)
Observational Study
The maternal microbiome plays a vital role in shaping pregnancy outcomes, but there remains a substantial gap in understanding its precise relationships to maternal health, particularly in relation to potential effects of body mass index (BMI) on gut microbial diversity. The aim of this observational study was to assess maternal characteristics in association with pre-pregnancy BMI and to further assess microbial diversity in association with specific maternal characteristics. Eighty-four pregnant women were recruited during their third trimester of pregnancy from various prenatal clinics across the state of Michigan. The participants completed an enrollment questionnaire including self-reported pre-pregnancy BMI; stool samples were collected to assess the fecal microbial community composition. Pre-pregnancy obesity (BMI 30+) was associated (univariably) with antibiotic use before pregnancy, ever smoked, lower education level, and being unmarried. The gut microbiota alpha diversity was significantly different for pregnant women by pre-pregnancy BMI category (normal, overweight, obese). The beta diversity was unique for the gut microbiotas of pregnant women within each BMI category, by education level, and by marital status. Multivariable models revealed that pre-pregnancy BMI, maternal education, marital status, and maternal age were associated with the microbial diversity of the gut microbiota during pregnancy. These results give new insight into the relationship between a woman's microbiome during pregnancy and their prenatal health, along with an understanding of the relationships between socioeconomic factors and microbial diversity.
Topics: Humans; Female; Pregnancy; Body Mass Index; Adult; Feces; Gastrointestinal Microbiome; Obesity; Michigan; Young Adult; Educational Status; Socioeconomic Factors; Pregnancy Trimester, Third
PubMed: 38931236
DOI: 10.3390/nu16121881 -
Nutrients Jun 2024Maternal obesity and/or Western diet (WD) is associated with an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven,...
Maternal obesity and/or Western diet (WD) is associated with an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by the dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition and was associated with a reduced abundance of in GF offspring. Further, the expression of was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of . Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, highlighting the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and the development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.
Topics: Animals; Gastrointestinal Microbiome; Female; Pregnancy; Diet, Western; Immunity, Innate; Tryptophan; Mice; Receptors, Aryl Hydrocarbon; Mice, Inbred C57BL; Interleukin-10; Prenatal Exposure Delayed Effects; Obesity, Maternal; Liver; Maternal Nutritional Physiological Phenomena; Male; Macrophages; Disease Models, Animal
PubMed: 38931163
DOI: 10.3390/nu16121808