Spatial Transcriptomics Analysis: Maternal Obesity Impairs Myogenic Cell Migration and Differentiation during Embryonic Limb Development.

Limb muscle is responsible for physical activities and myogenic cell migration during embryogenesis is indispensable for limb muscle formation. Maternal obesity (MO) impairs prenatal skeletal muscle development, but the effects of MO on myogenic cell migration remain to be examined. C57BL/6 mice embryos were collected at E13.5. The GeoMx DSP platform was used to customize five regions along myogenic cell migration routes (myotome, dorsal/ventral limb, limb stroma, limb tip), and data were analyzed by GeomxTools 3.6.0. A total of 2224 genes were down-regulated in the MO group. The GO enrichment analysis showed that MO inhibited migration-related biological processes. The signaling pathways guiding myogenic migration such as hepatocyte growth factor signaling, fibroblast growth factor signaling, Wnt signaling and GTPase signaling were down-regulated in the MO E13.5 limb tip. Correspondingly, the expression levels of genes involved in myogenic cell migration, such as Pax3, Gab1, Pxn, Tln2 and Arpc, were decreased in the MO group, especially in the dorsal and ventral sides of the limb. Additionally, myogenic differentiation-related genes were down-regulated in the MO limb. MO impedes myogenic cell migration and differentiation in the embryonic limb, providing an explanation for the impairment of fetal muscle development and offspring muscle function due to MO.

Glucose intolerance as a consequence of hematopoietic stem cell dysfunction in offspring of obese mice.

OBJECTIVE: Maternal obesity is increasingly common and negatively impacts offspring health. Children of mothers with obesity are at higher risk of developing diseases linked to hematopoietic system abnormalities and metabolism such as type 2 diabetes. Interestingly, disease risks are often dependent on the offspring's sex, suggesting sex-specific reprogramming effect of maternal obesity on offspring hematopoietic stem and progenitor cell (HSPC) function. However, the impact of maternal obesity exposure on offspring HSPC function, and the capability of HSPC to regulate offspring metabolic health is largely understudied. This study aims to test the hypothesis that offspring of obese mice exhibit sex-differences in HSPC function that affect offspring's metabolic health. METHODS: We first assessed bone marrow hematopoietic stem and progenitor cell phenotype using postnatal day 21 (P21) and 8-week-old C57BL/6J mice born to control and diet-induced obese dams. We also sorted HSPC (Lineage-, Sca1+, cKit + cells) from P21 mice for competitive primary and secondary transplant, as well as transcriptomic analysis. Body weight, adiposity, insulin tolerance test and glucose tolerance tests were performed in primary and secondary transplant recipient animals. RESULTS: We discovered sex-differences in offspring HSPC function in response to maternal obesity exposure, where male offspring of obese dams (MatOb) showed decreased HSPC numbers and engraftment, while female MatOb offspring remained largely unaffected. RNA-seq revealed immune stimulatory pathways in female MatOb offspring. Finally, only recipients of male MatOb offspring HSPC exhibited glucose intolerance. CONCLUSIONS: This study demonstrated the lasting effect of maternal obesity exposure on offspring HSPC function and implicates HSPC in metabolic regulation.

Maternal Overweight and Obesity and Their Effect on the Growth of the Newborn During the First Six Months of Life.

INTRODUCTION:  Maternal overweight and obesity during pregnancy have been shown to have multiple negative effects on the mother's health, which can even affect the infant's growth by increasing weight gain and altering various indicators, such as weight for age, length for age and weight for length. While breast milk on the other hand reduces these risks, and it's the best and most complete food for the newborn. It's a dynamic fluid capable of being modified to meet the needs of each stage of the newborn, but despite this capacity and the fact that maternal body mass index can have an impact on its components, through complex biological mechanisms, it manages to reduce the negative effects accumulated during pregnancy and even promotes a healthy state in the baby. In a country like Mexico, where overweight and obesity affect a large part of the population, it is important to study their causes and which could be the effect of this increased maternal overweight during pregnancy and lactation on newborns. OBJECTIVE: Identify the alterations associated with increased maternal body mass index during pregnancy and breastfeeding on mothers' health and their possible effect on the growth of the newborn during the first six months of life. MATERIAL AND METHODS: This was a prospective cohort study. Forty-two healthy binomials (mother and child), without problems during delivery and without serious illnesses during the breastfeeding period, were included. Maternal body mass index at the beginning of pregnancy allowed us to create two comparison groups between mothers: one with adequate weight, another with overweight or obesity. Follow-up was carried out once a month during the first six months of life, evaluating the somatometric development of mothers and children. All mothers completed the six-month period of exclusive breastfeeding. RESULTS:  There were differences between both groups of women. The one that included overweight and obese women compared to the group of women with adequate weight had a higher number of pregnancies, abortions, plasma glucose levels in the third trimester of pregnancy, and a lower number of prenatal control visits and plasma platelet levels (all with p<0.05). Regarding the baby's growth, there was a difference between the weight for length classification at 60-, 120-, 150- and 180-day follow-ups. The group to which the mother was assigned with respect to her body mass index at the beginning of pregnancy (adequate weight group and overweight/obese group) was the only factor associated with the risk of the baby being overweight according to weight for length indicator at the 180-day follow-up, with an OR = 5.2 (95%CI 1.02-26.59). CONCLUSIONS: Maternal overweight and obesity during pregnancy have a negative effect on the mother's health and baby's weight gain in its weight-for-length classification during the first six months of life. Although breastfeeding has been shown to have a positive effect on the growth of the baby, exposure to a higher maternal body mass index during pregnancy triggers important metabolic alterations that promote the development of diseases. It is important to establish weight control guidelines in women who wish to become pregnant to reduce the negative effects on the mother and offspring.

Diet-Induced Obesity in Mice Affects the Maternal Gut Microbiota and Immune Response in Mid-Pregnancy.

Maternal obesity during pregnancy is associated with adverse pregnancy outcomes. This might be due to undesired obesity-induced changes in the maternal gut microbiota and related changes in the maternal immune adaptations during pregnancy. The current study examines how obesity affects gut microbiota and immunity in pregnant obese and lean mice during mid-pregnancy (gestational day 12 (GD12)). C57BL/6 mice were fed a high-fat diet or low-fat diet from 8 weeks before mating and during pregnancy. At GD12, we analyzed the gut microbiota composition in the feces and immune responses in the intestine (Peyer's patches, mesenteric lymph nodes) and the peripheral circulation (spleen and peripheral blood). Maternal obesity reduced beneficial bacteria (e.g., Bifidobacterium and Akkermansia) and changed intestinal and peripheral immune responses (e.g., dendritic cells, Th1/Th2/Th17/Treg axis, monocytes). Numerous correlations were found between obesity-associated bacterial genera and intestinal/peripheral immune anomalies. This study shows that maternal obesity impacts the abundance of specific bacterial gut genera as compared to lean mice and deranges maternal intestinal immune responses that subsequently change peripheral maternal immune responses in mid-pregnancy. Our findings underscore the opportunities for early intervention strategies targeting maternal obesity, ideally starting in the periconceptional period, to mitigate these obesity-related pregnancy effects.

Both Maternal High-Fat and Post-Weaning High-Carbohydrate Diets Increase Rates of Spontaneous Hepatocellular Carcinoma in Aged-Mouse Offspring.

Both maternal obesity and postnatal consumption of obesogenic diets contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). However, there is no consensus as to whether diets that are high in fat or carbohydrates/sugars differentially influence the development of HCC. Moreover, the long-term effects of prenatal HF exposure on HCC and whether this is influenced by postnatal diet has not yet been evaluated. C57BL/6 dams were fed either a low-fat, high-carbohydrate control (C) or low-carbohydrate, high-fat (HF) diet. At weaning, male and female offspring were fed the C or HF diet, generating four diet groups: C/C, C/HF, HF/C and HF/HF. Tissues were collected at 16 months of age and livers were assessed for MASLD and HCC. Glucose regulation and pancreatic morphology were also evaluated. Liver tissues were assessed for markers of glycolysis and fatty acid metabolism and validated using a human HCC bioinformatic database. Both C/HF and HF/HF mice developed obesity, hyperinsulinemia and a greater degree of MASLD than C/C and HF/C offspring. However, despite significant liver and pancreas pathology, C/HF mice had the lowest incidence of HCC while tumour burden was highest in HF/C male offspring. The molecular profile of HCC mouse samples suggested an upregulation of the pentose phosphate pathway and a downregulation of fatty acid synthesis and oxidation, which was largely validated in the human dataset. Both pre-weaning HF diet exposure and post-weaning consumption of a high-carbohydrate diet increased the risk of developing spontaneous HCC in aged mice. However, the influence of pre-weaning HF feeding on HCC development appeared to be stronger in the context of post-weaning obesity. As rates of maternal obesity continue to rise, this has implications for the future incidence of HCC and possible dietary manipulation of offspring carbohydrate intake to counteract this risk.

Maternal high fat-high energy diet alters metabolic factors in the non-human primate fetal heart.

The consumption of high fat-high energy diets (HF-HEDs) continues to rise worldwide and parallels the rise in maternal obesity (MO) that predisposes offspring to cardiometabolic disorders. Although the underlying mechanisms are unclear, thyroid hormones (TH) modulate cardiac maturation in utero. Therefore, we aimed to determine the impact of a high fat-high energy diet (HF-HED) on the hormonal, metabolic and contractility profile of the non-human primate (NHP) fetal heart. At ∼9 months preconception, female baboons (Papio hamadryas) were randomly assigned to either a control diet or HF-HED. At 165 days gestational age (term = 184 days), fetuses were delivered by Caesarean section under anaesthesia, humanely killed, and left ventricular cardiac tissue (Control (n = 6 female, 6 male); HF-HED (n = 6 F, 6 M)) was collected. Maternal HF-HED decreased the concentration of active cardiac TH (i.e. triiodothyronine (T3)), and type 1 iodothyronine deiodinase (DIO1) mRNA expression. Maternal HF-HED decreased the abundance of cardiac markers of insulin-mediated glucose uptake phosphorylated insulin receptor substrate 1 (Ser789) and glucose transporter 4, and increased protein abundance of key oxidative phosphorylation complexes (I, III, IV) and mitochondrial abundance in both sexes. Maternal HF-HED alters cardiac TH status, which may induce early signs of cardiac insulin resistance. This may increase the risk of cardiometabolic disorders in later life in offspring born to these pregnancies. KEY POINTS: Babies born to mothers who consume a high fat-high energy diet (HF-HED) prior to and during pregnancy are predisposed to an increased risk of cardiometabolic disorders across the life course. Maternal HF-HED prior to and during pregnancy decreased thyroid hormone triiodothyronine (T3) concentrations and type 1 iodothyronine deiodinase DIO1 mRNA expression in the non-human primate fetal heart. Maternal HF-HED decreased markers of insulin-dependent glucose uptake, phosphorylated insulin receptor substrate 1 and glucose transporter 4 in the fetal heart. Maternal HF-HED increased mitochondrial abundance and mitochondrial OXPHOS complex I, III and IV in the fetal heart. Fetuses from HF-HED pregnancies are predisposed to cardiometabolic disorders that may be mediated by changes in T3, placing them on a poor lifetime cardiovascular health trajectory.

Precision Interventions Targeting the Maternal Metabolic Milieu for Healthy Pregnancies in Obesity.

PURPOSE OF REVIEW: Entering pregnancy with obesity increases the risk of adverse health outcomes for parent and child. As such, research interventions are largely focused on limiting excess gestational weight gain during pregnancy, especially in those with obesity. Yet, while many lifestyle interventions are successful in reducing GWG, few affect pregnancy outcomes. Here we review work targeting the metabolic milieu instead of focusing solely on weight. RECENT FINDINGS: Work done in non-pregnant populations suggests that specifically targeting glucose, triglyceride, and leptin levels or inflammatory makers improves the metabolic milieu and overall health. We posit that precision interventions that include strategies such as time restricted eating, following the 24 h movement guidelines, or reducing sedentary behavior during pregnancy can be successful approaches benefiting the maternal metabolic milieu and minimize the risk of adverse pregnancy outcomes. Personalized tools such as continuous glucose monitors or community-based approaches play an important role in pre-conception health and should be extrapolated to pregnancy interventions to directly benefit the metabolic milieu optimizing health outcomes for both parent and child.

Pre-delivery BMI and the Accuracy of Fetal Weight Estimation in Very Preterm Infants.

OBJECTIVES: To examine the relation between maternal pre-delivery BMI and the accuracy of sonographic estimated fetal weight (EFW) in very preterm infants (<32 weeks gestation). METHODS: This retrospective study included singleton infants born between January 2010 and March 2023, at gestational ages 230 to 316 weeks, at a tertiary university-affiliated hospital. Absolute weight, percentage error, absolute percentage error, and overestimation and underestimation of EFW were compared between women with pre-delivery normal weight (BMI 18.5-24.99 kg/m2), overweight (BMI 25.0-29.99 kg/m2), and obesity (BMI >35.0 kg/m2). Multivariate linear regression analyses adjusted for potential confounders were performed to assess relations of maternal pre-conception and of pre-delivery BMI, with EFW accuracy. RESULTS: Included were 286 pregnancies. The absolute difference, percentage error, absolute percentage error, error within the 10% range, and underestimation or overestimation of EFW were similar between the groups. The multivariate linear regression analyses did not show significant associations of pre-conceptional BMI or of pre-delivery BMI with the percentage error. However, for small for gestational age compared to appropriate for gestational age fetuses, the percentage error was greater (8.9% vs. -0.6%, ß = 0.35, P < 0.001) and the absolute percentage error was greater (11.0% vs. 6.7%, P < 0.001). Small for gestational age fetuses were at risk of fetal weight overestimation (percentage error exceeding 15%); OR 7.20 (95% CI 2.91-17.80). CONCLUSIONS: Maternal pre-delivery BMI was not found to be related to EFW accuracy in very preterm infants. Nevertheless, EFW should be interpreted carefully, as it may underdiagnose poor fetal growth in this population.

Examining rurality and social determinants of health among women with GDM: a 15-year comprehensive population analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication with long-term health consequences for mothers and their children. The escalating trends of GDM coupled with the growing prevalence of maternal obesity, a significant GDM risk factor projected to approach nearly 60% by 2030 in Kansas, has emerged as a pressing public health issue. METHODS: The aim of this study was to compare GDM and maternal obesity trends in rural and urban areas and investigate maternal demographic characteristics influencing the risk of GDM development over a 15-year period. Trend analyses and a binary logistic regression were employed utilizing 2005 to 2019 de-identified birth record vital statistics from the Kansas Department of Health and Environment (N = 589,605). RESULTS: Over the cumulative 15-year period, a higher prevalence of GDM was observed across age, race/ethnicity, education, and insurance source. Throughout this period, there was an increasing trend in both GDM and obese pre-pregnancy BMI age-adjusted prevalence, with noticeable rural-urban disparities. From 2005 to 2019, women, including Asians (OR: 2.73, 95% CI 2.58%-2.88%), American Indian or Alaskan Natives (OR: 1.58, 95%, CI 1.44-1.73%), Hispanics (OR: 1.42, 95% CI 1.37%-1.48%), women residing in rural areas (OR: 1.09, 95%, CI 1.06-1.12%), with advanced maternal age (35-39 years, OR: 4.83 95% CI 4.47%-5.22%; ≥40 years, OR: 6.36 95%, CI 5.80-6.98%), with lower educational status (less than high school, OR: 1.15, 95% CI 1.10%-1.20%; high school graduate, OR: 1.10, 95% CI 1.06%-1.13%), Medicaid users (OR: 1.10, 95% CI 1.06%-1.13%), or with an overweight (OR: 1.78, 95% CI 1.72%-1.84%) or obese (OR: 3.61, 95% CI 3.50%-3.72%) pre-pregnancy BMI were found to be at an increased risk of developing GDM. CONCLUSIONS: There are persistent rural-urban and racial/ethnic disparities present from 2005 to 2019 among pregnant women in Kansas with or at-risk of GDM. There are several socioeconomic factors that contribute to these health disparities affecting GDM development. These findings, alongside with prominent rising maternal obesity trends, highlight the need to expand GDM services in a predominantly rural state, and implement culturally-responsive interventions for at-risk women.

Obesity and diet independently affect maternal immunity, maternal gut microbiota and pregnancy outcome in mice.

Introduction: Maternal obesity poses risks for both mother and offspring during pregnancy, with underlying mechanisms remaining largely unexplored. Obesity is associated with microbial gut dysbiosis and low-grade inflammation, and also the diet has a major impact on these parameters. This study aimed to investigate how maternal obesity and diet contribute to changes in immune responses, exploring potential associations with gut microbiota dysbiosis and adverse pregnancy outcomes in mice. Methods: Before mating, C57BL/6 mice were assigned to either a high-fat-diet (HFD) or low-fat-diet (LFD) to obtain obese (n=17) and lean (n=10) mice. To distinguish between the effects of obesity and diet, 7 obese mice were switched from the HFD to the LFD from day 7 until day 18 of pregnancy ("switch group"), which was the endpoint of the study. T helper (Th) cell subsets were studied in the spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP), while monocyte subsets and activation status were determined in maternal blood (flow cytometry). Feces were collected before and during pregnancy (day 7,14,18) for microbiota analysis (16S rRNA sequencing). Pregnancy outcome included determination of fetal and placental weight. Results: Obesity increased splenic Th1 and regulatory T cells, MLN Th1 and PP Th17 cells and enhanced IFN-γ and IL-17A production by splenic Th cells upon ex vivo stimulation. Switching diet decreased splenic and PP Th2 cells and classical monocytes, increased intermediate monocytes and activation of intermediate/nonclassical monocytes. Obesity and diet independently induced changes in the gut microbiota. Various bacterial genera were increased or decreased by obesity or the diet switch. These changes correlated with the immunological changes. Fetal weight was lower in the obese than the lean group, while placental weight was lower in the switch than the obese group. Discussion: This study demonstrates that obesity and diet independently impact peripheral and intestinal immune responses at the end of pregnancy. Simultaneously, both factors affect specific bacterial gut genera and lead to reduced fetal or placental weight. Our data suggest that switching diet during pregnancy to improve maternal health is not advisable and it supports pre/probiotic treatment of maternal obesity-induced gut dysbiosis to improve maternal immune responses and pregnancy outcome.

Maternal obesity alters fetal neuroinflammation in a murine model of preterm birth.

BACKGROUND: Preterm birth from intrauterine infection is a leading cause of neonatal neurologic morbidity. Likewise, maternal obesity is associated with intra-amniotic infection and inflammation. Whether maternal obesity is a risk factor for fetal brain injury that occurs with premature birth remains unknown. This study hypothesized that maternal obesity intensifies fetal neuroinflammation in the setting of premature delivery. OBJECTIVE: This study aimed to examine the influence of maternal obesity on perinatal neuroinflammatory responses that arise with preterm birth using a murine model. STUDY DESIGN: Dams with obesity were generated via a high-fat diet that was maintained throughout pregnancy. In parallel, dams without obesity (normal) received a control diet. All dams were paired with males on normal diet. Pregnant dams were randomized to receive an intrauterine administration of bacterial endotoxin (lipopolysaccharide) or the vehicle (phosphate-buffered saline) on embryo day 15.5 of what is typically a 19- to 21-day gestation. Fetal brains were harvested 6 hours after intrauterine administrations, and the expressions of key inflammatory cytokines (Il1b, Il6, and Tnf) and panels of metabolic, immune, and inflammatory genes were analyzed. RESULTS: With the phosphate-buffered saline, there was no difference in gene expression related to maternal obesity. There were substantial differences in Il6 and immune/inflammatory expression profiles in fetal brains from dams with obesity vs normal dams that received lipopolysaccharide. Few differences were observed among the metabolic genes examined under these conditions. The gene expression pattern associated with maternal obesity correlated with pathways related to white matter injury. CONCLUSION: The expression of neuroinflammatory markers instigated by bacterial endotoxin via intrauterine lipopolysaccharide was greater in embryo brains obtained from dams with obesity. Expression profiles suggest that in combination with intrauterine inflammation, maternal obesity may increase the risk of fetal white matter injury. Further investigation is warranted to understand the relationship between maternal health and neurologic outcomes associated with prematurity.

Differing intensities of a midwife-led antenatal healthy lifestyle service on maternal and neonatal outcomes: A retrospective cohort study.

INTRODUCTION: Maternal obesity and excessive gestational weight gain are associated with adverse maternal and neonatal outcomes. There is uncertainty over the most effective antenatal healthy lifestyle service, with little research determining the impact of different lifestyle intervention intensities on pregnancy outcomes. METHOD: This retrospective cohort study compared pregnancy and birth outcomes in women with a body mass index of 40 or above who were offered a low intensity midwife-led antenatal healthy lifestyle service (one visit) with women who were offered an enhanced service (three visits). The primary outcome was gestational weight gain. RESULTS: There were no differences between the two healthy lifestyle service intensities (N = 682) in the primary outcome of mean gestational weight gain [adjusted mean difference (aMD) -1.1 kg (95 % CI -2.3 to 0.1)]. Women offered the enhanced service had lower odds of gaining weight in excess of Institute of Medicine recommendations [adjusted odds ratio (aOR) 0.63 (95 % CI 0.40-0.98)] with this reduction mainly evident in multiparous women. Multiparous women also gained less weight per week [aMD -0.06 kg/week (95 % CI -0.11 to -0.01)]. No overall beneficial effects were seen in maternal or neonatal outcomes measured such as birth weight [aMD 25 g (95 % CI -71 to 121)], vaginal birth [aOR 0.87 (95 % CI 0.64-1.19)] or gestational diabetes mellitus [aOR 1.42 (95 % CI 0.93-2.17)]. However, multiparous women receiving the enhanced service had reduced odds of small for gestational age [aOR 0.52 (95 % CI 0.31-0.87)]. This study was however underpowered to detect differences in some outcomes with low incidences. DISCUSSION: Uncertainty remains over the best management of women with severe obesity regarding effective interventions in terms of intensity. It is suggested that further research needs to consider the different classes of obesity separately and have a particular focus on the needs of nulliparous women given the lack of effectiveness of this service among these women.

A systematic review of MRI studies on the effects of maternal obesity on offspring brain structure and function.

Maternal obesity before or during pregnancy has been associated previously in offspring with a wide range of poor neurodevelopmental outcomes and mental health problems. The effects of maternal obesity on offspring brain structure and function that may be responsible for these poor outcomes are not well understood. We, therefore, undertook a systematic review of magnetic resonance imaging (MRI) studies that have assessed the associations of maternal obesity with brain measures in offspring. A systematic search was conducted in PubMed, Web of Science, Scopus, and PsycINFO on August 20, 2023. Of 15 eligible studies, seven employed functional MRI (fMRI), five diffusion tensor imaging (DTI), and four anatomical MRI (one used both DTI and anatomical MRI) in the offspring. The ages of offspring varied widely: one was a study of fetuses in utero, five of neonates, one of infants, five of school-aged children, two of both neonates and infants, and one of both children and adults. Collectively, 12 studies reported significant associations of maternal obesity with structural or functional alterations of the offspring's brain, most frequently in the prefrontal cortex and limbic system. In conclusion, maternal obesity appears to have a profound influence on offspring brain development, particularly within the prefrontal and limbic networks that regulate emotion and behavior. Further studies are needed to identify how changes in brain structure and function mediate the effects of maternal obesity on long-term emotional and behavioral outcomes, as well as the molecular pathways through which maternal obesity alters offspring brain development.

Grandmaternal pre-pregnancy body mass index and infant birthweight: a mediation analysis of maternal pre-pregnancy body mass index.

The objectives of this study were to examine the total effect of grandmaternal [G0] pre-pregnancy body mass index (BMI) on infant [G2] birthweight z-score and to quantify the mediation role of maternal [G1] pre-pregnancy BMI. Data were extracted from the Nova Scotia 3G Multigenerational Cohort. The association between G0 pre-pregnancy BMI and G2 birthweight z-score and the mediated effect by G1 pre-pregnancy BMI were estimated using g-computation with adjustment for confounders identified using a directed acyclic graph and accounting for intermediate confounding. 20822 G1-G2 dyads from 18450 G0 were included. Relative to G0 normal weight, G0 underweight decreased mean G2 birthweight z-score (-0.11, 95% confidence interval (CI) -0.20, -0.030), while G0 overweight and obesity increased mean G2 birthweight z-score (0.091 [95% CI 0.034, 0.15] and 0.22 [95% CI 0.11, 0.33]). G1 pre-pregnancy BMI partly mediated the association, with the largest effect size observed for G0 obesity (0.11, 95% CI 0.080, 0.14). Estimates of the direct effect were close to the null. In conclusion, grandmaternal pre-pregnancy BMI was associated with infant birthweight z-score. Maternal pre-pregnancy BMI partly mediated the association, suggesting that factors related to BMI may play an important role in the transmission of weight across the maternal line.

Assessing Moroccan physician knowledge and practices regarding maternal obesity's impact on childhood obesity: Implications for prevention and intervention.

BACKGROUND: Childhood obesity is a growing global concern with far-reaching health implications. This study focuses on evaluating the knowledge and practices of physicians in Morocco regarding the link between maternal obesity and childhood obesity. Despite the increasing prevalence of childhood obesity worldwide, this issue remains inadequately addressed in the Moroccan context. AIM: To assess the awareness and practices of physicians in Morocco concerning the connection between maternal obesity and childhood obesity. METHODS: The research encompasses a comprehensive survey of practicing physicians, revealing significant gaps in awareness and practices related to maternal obesity. RESULTS: Notably, a significant portion of doctors do not provide adequate guidance to overweight pregnant women, highlighting the urgency for targeted educational programs. CONCLUSION: In conclusion, this research illuminates critical areas for improvement in tackling childhood obesity in Morocco. By addressing these gaps, fostering awareness, and enhancing medical practices, the healthcare system can contribute significantly to preventing childhood obesity and improving the overall health of future generations.

Postpartum Obesity Is Associated With Increases in Child Adiposity in Midchildhood in a Cohort of Black and Dominican Youth.

Background: Obesity disproportionately affects marginalized and low-income populations. Birth parent obesity from the prenatal period and childhood has been associated with child obesity. It is unknown whether prenatal or postnatal birth parent obesity has differential effects on subsequent changes in adiposity and metabolic health in children. Objectives: We evaluated how birth parent obesity 7 y after delivery was associated with child body composition changes and cardiometabolic health in midchildhood and further assessed the influence of the perinatal and postpartum period on associations. Methods: Black and Dominican pregnant individuals were enrolled, and dyads (n = 319) were followed up at child age 7 and 9 y. Measures included, height, weight, waist circumference (WC), and percent body fat (BF%). Multiple linear regression was used to relate postpartum weight status with child outcomes accounting for attrition, and a series of secondary analyses were conducted with additional adjustment for perinatal weight status, gestational weight gain (GWG), and/or long-term weight retention to evaluate how these factors influenced associations. Results: Almost one-quarter (23%) of birth parents and 24.1% children were classified with obesity at child age 7 y, while at 9 y, 30% of children had obesity. Birth parent obesity at child age 7 y was associated with greater changes, from ages 7 to 9 y, in child BMI z-score (ß: 0.13; 95% CI: 0.02, 0.24) and BF% (ß: 1.15; 95% CI: 0.22, 2.09) but not obesity at age 9 y. All observed associations crossed the null after additional adjustment for prenatal factors. Conclusions: Birth parent obesity at 7-y postpartum is associated with greater gains in child BMI z-score and BF% in midchildhood. These associations diminish after accounting for prenatal size, suggesting a lasting impact of the perinatal environment and that interventions supporting families from the prenatal period through childhood are needed.

Childhood obesity from the genes to the epigenome.

The prevalence of obesity and its associated comorbidities has surged dramatically in recent decades. Especially concerning is the increased rate of childhood obesity, resulting in diseases traditionally associated only with adulthood. While obesity fundamentally arises from energy imbalance, emerging evidence over the past decade has revealed the involvement of additional factors. Epidemiological and murine studies have provided extensive evidence linking parental obesity to increased offspring weight and subsequent cardiometabolic complications in adulthood. Offspring exposed to an obese environment during conception, pregnancy, and/or lactation often exhibit increased body weight and long-term metabolic health issues, suggesting a transgenerational inheritance of disease susceptibility through epigenetic mechanisms rather than solely classic genetic mutations. In this review, we explore the current understanding of the mechanisms mediating transgenerational and intergenerational transmission of obesity. We delve into recent findings regarding both paternal and maternal obesity, shedding light on the underlying mechanisms and potential sex differences in offspring outcomes. A deeper understanding of the mechanisms behind obesity inheritance holds promise for enhancing clinical management strategies in offspring and breaking the cycle of increased metabolic risk across generations.

Breastfeeding Practices and Postpartum Weight Retention in an Asian Cohort.

This study examines relationships between breastfeeding practices and postpartum weight retention (PPWR) at 6 and 12 months postpartum among 379 first-time mothers participating in a clinical trial in Singapore. We categorized feeding modes at 6 months into exclusive breastfeeding, mixed feeding, and exclusive formula feeding. Participants were analyzed in two groups based on their PPWR assessment at 6 and 12 months postpartum, with complete datasets available for each assessment. We calculated PPWR by subtracting pre-pregnancy weight from self-reported weight at 6 and 12 months postpartum, defining substantial PPWR as ≥5 kg retention. Modified Poisson regression models adjusted for potential confounders were performed. At 6 and 12 months, 35% (n = 132/379) and 31% (n = 109/347) of women experienced substantial PPWR, respectively. Compared to exclusive breastfeeding, mixed feeding (risk ratio 1.85; 95% confidence interval 1.15, 2.99) and exclusive formula feeding (2.11; 1.32, 3.28) were associated with a higher risk of substantial PPWR at 6 months. These associations were slightly attenuated at 12 months and appeared stronger in women with pre-pregnancy overweight or obesity. This study suggests that breastfeeding by 6 months postpartum may help mitigate PPWR, particularly with exclusive breastfeeding. It also draws attention to targeted interventions to promote breastfeeding among women with overweight or obesity.

Impact of diet-induced maternal obesity on the reproductive capacity of F1 female offspring and the early development of the second generation.

The aim of this study was to examine the impact of maternal obesity on the reproductive capacity of the female offspring (F1) and on the early development of the second generation (F2). To this end, rats were fed either standard (SD) or cafeteria (CD) diet. CD rats and their offspring were divided into 2 groups: rats with 18% and ≥25% overweight (CD18 and CD25, respectively) and offspring from CD18 and CD25 rats (OCD18 and OCD25, respectively). Both OCD groups achieved greater weight gain than controls, without changes in the serum levels of glucose, cholesterol or triglycerides. However, they showed increased gonadal cholesterol concentration and fat content compared to controls. Female OCD groups showed a slight prolongation of the estrous cycle and different pattern of changes in the weight gain during pregnancy. The OCD25 group displayed an increased fertility index and preimplantation losses, and changes in some fetal measurements. Some OCD25 dams gave birth to a larger litter of pups and displayed a lower viability index and lactation rate than controls. OCD25 dams also showed an increase in estradiol and a decrease in testosterone and anti-Müllerian hormone. OCD25 rats showed increased mRNA levels of steroidogenenic enzymes. The offspring from OCD25 females (F2OCD25 offspring) showed early vaginal opening and higher ovulation rate in females, and lower ano-genital distances in males, compared to controls. In conclusion, these results reflect that maternal obesity impacts on the reproductive health of successive generations, probably as a result of epigenetic changes in different systems, including germ cells.

Maternal high-fat diet-induced microbiota changes are associated with alterations in embryonic brain metabolites and adolescent behaviour.

The developing central nervous system is highly sensitive to nutrient changes during the perinatal period, emphasising the potential impact of alterations of maternal diet on offspring brain development and behaviour. A growing body of research implicates the gut microbiota in neurodevelopment and behaviour. Maternal overweight and obesity during the perinatal period has been linked to changes in neurodevelopment, plasticity and affective disorders in the offspring, with implications for microbial signals from the maternal gut. Here we investigate the impact of maternal high-fat diet (mHFD)-induced changes in microbial signals on offspring brain development, and neuroimmune signals, and the enduring effects on behaviour into adolescence. We first demonstrate that maternal caecal microbiota composition at term pregnancy (embryonic day 18: E18) differs significantly in response to maternal diet. Moreover, mHFD resulted in the upregulation of microbial genes in the maternal intestinal tissue linked to alterations in quinolinic acid synthesis and elevated kynurenine levels in the maternal plasma, both neuronal plasticity mediators related to glutamate metabolism. Metabolomics of mHFD embryonic brains at E18 also detected molecules linked to glutamate-glutamine cycle, including glutamic acid, glutathione disulphide, and kynurenine. During adolescence, the mHFD offspring exhibited increased locomotor activity and anxiety-like behaviour in a sex-dependent manner, along with upregulation of glutamate-related genes compared to controls. Overall, our results demonstrate that maternal exposure to high-fat diet results in microbiota changes, behavioural imprinting, altered brain metabolism, and glutamate signalling during critical developmental windows during the perinatal period.