Advertisement

Sign up for our daily newsletter

Advertisement

Maternal obesity and heart disease in the offspring torrent – Association of Gestational Weight Gain With Adverse Maternal and Infant Outcomes

Biosci Rep 38 2 : BSR The fetal glucose steal: an underappreciated phenomenon in diabetic pregnancy.

Matthew Cox
Monday, March 8, 2021
Advertisement
  • Values represent the absolute risks of any adverse maternal and infant outcome left panel and the percentages of participants right panel for each combination of body mass index and gestational weight gain.

  • Though often associated with fetal overgrowth, maternal obesity can also conversely be associated with increased risk of premature birth and low birth weight, with implications for renal development and CKD risk [ 67 ]. The current review will discuss the evidence for the role of maternal obesity in the developmental programming of chronic metabolic disease in offspring, particularly focussing on the role of fetal programming in the development of CKD.

  • The current article gives an overview of pathophysiological changes associated with maternal obesity and their consequences on placental structure and function.

  • For participants without information on pre-pregnancy BMI 4.

Associated Data

Eur J Clin Nutr SHBG could represent an integrating biomarker for an adverse cardio-metabolic profile in pregnant women with pregestational plus gestational obesity. To substantiate existing evidence of clinical studies, more large-scale clinical trials are necessary.

Findings from the unadjusted models were similar to the findings from the adjusted models and therefore are not presented separately. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Statistical Analysis. Create a free personal account to make a comment, download free article PDFs, sign up for alerts and more. Clin Sci.

ALSO READ: Obese Kids Pics

Thereafter, a large randomized, controlled trial carried out in the Gambian communities demonstrated the powerful effect of periconceptional maternal nutrition on DNA methylation in offspring blood and hair and was predicted msternal periconceptional maternal plasma concentrations of key micronutrients, such as homocysteine, folate, and B vitamins [ ]. Samuelsson heart disease al. Pollock, Disfase Saad; Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring. Maternal age at delivery, socioeconomic status, offspring sex, birth weight, gestation at delivery, and gestation at measurement of BMI. There are several unanswered questions related to this concept. Mitochondria are intracellular organelles extensively involved in cellular metabolism and oxidative stress defense as a result of inevitable free radical leakage in the process of cellular respiration. Although genetic predisposition and postnatal environment are key features for the development of chronic disease, there appears to be a critical window during gestation which influences the long-term risk unaccounted for by genetic tendency and postnatal environment alone.

In fact, the placenta also has the ability matrnal re-esterify and store lipids for later fetal use [ 99 ]. An imbalance between reactive oxygen species and antioxidant defense mechanisms leads to cellular damage via oxidative stress. The placenta is highly permeable to free fatty acids, transfer of which is gradient dependent. Maternal obesity programs metabolic disease in offspring. Google Scholar. Furthermore, in the setting of a large maternal—fetal glucose gradient, maternal postprandial glucose peaks may even be blunted further exacerbating the fetal exposure to glucose though masking the phenomenon in the mother.

DNA Methylation Signatures in Placenta and Umbilical Cord: Association with Maternal Obesity

Table 2 summarizes some examples of long-term studies using various species to model maternal obesity. A limitation of the existing data regarding the effects of maternal obesity on metabolic health is that few studies, both in humans and animal models, have specifically examined the effect of maternal obesity on renal health in offspring. Rivera et al.

  • Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy. Fionnuala M.

  • A Swedish cohort including 2, live singleton infants born between and was analyzed. Obesity is associated with chronic low-grade inflammation largely mediated by excess adipose tissue [ ].

  • Quiz Ref ID The observed results were similar after adjustment for gestational age at birth and after excluding preterm births.

  • Changes in blood glucose regulation and blood pressure by maternal obesity or postnatal insults may also have contributed to the renal effects. Published by Elsevier Inc.

Mitochondrial dysfunction in oocytes of obese mothers: transmission to offspring and reversal by pharmacological endoplasmic reticulum stress inhibitors. Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 person years. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Forsen et al. The kidneys of offspring of obese compared with lean mothers examined at Day 20, Week 9 and through to Week 32 showed persistent evidence of inflammation, oxidative stress, and fibrosis.

Data Availability Data from 37 different cohorts with different data publishing policies were used. What do these findings mean? Common aand disorders, including gestational diabetes and gestational hypertensive disorders, have also been related to offspring obesity risk [ 29 — 31 ]. In our study, fewer cohorts reached the age for the late childhood analyses than for the early or mid childhood analyses. Accessed October 25, Methods and findings We conducted an individual participant data meta-analysis of data frommothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. Epigenetic studies in developmental origins of health and disease: pitfalls and key considerations for study design and interpretation.

  • MiRNAs are involved in the regulation of biological processes, including differentiation, cell proliferation and energy metabolism [ 86 ]. Arch Gynecol Obstet.

  • Maternal obesity and the developmental programming of hypertension: a role for leptin.

  • The fetal over-nutrition hypothesis suggests that increased fetal exposure to nutrients may lead to persistent adaptations in the structure and function of adipose tissue, appetite regulation, and energy metabolism, leading to an increased susceptibility to later obesity [ 2425 ]. This is a credible question since a DNA methylation status change in fetal cord blood from obese pregnant women is correlated with maternal BMI, which alters fetal development through activating an involved inflammatory signaling pathway [ 2728 ].

  • Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 person years. Gestational weight gain in relation to offspring body mass index and obesity from infancy through adulthood.

Early postnatal life as a critical time window for determination of long-term metabolic health. Health Technol Assess. Zamore P. B PSG gene cluster located on human chromosome 19q13 analysis demonstrating a reciprocal increase in 5mC and decrease in 5hmC.

Williams L. Differences in design and study populations could account for the disparity in the reported results. Description of exposures and general characteristics per cohort eTable 6. Maternal pregnancy information was selected strictly from medical records. Thorkild I.

Introduction

Post-weaning diet determines metabolic risk in mice exposed to overnutrition in early life. When the agouti gene is in its normal methylated state, the coat is brown and offsppring mouse has low risk of metabolic disease. Low-density lipoprotein LDL and free fatty acids are all increased in obese compared with normal weight pregnant women [ 98 ]. There was an additive effect of maternal overnutrition to increase insulin levels in males. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring.

Therefore, characterizing the miRNA expression profiles of umbilical cord fetal blood samples maternal obesity and heart disease in the offspring torrent insight into the role that this epigenetic modulator has in controlling the gene expression patterns determining fetal development. A sustained dietary change increases epigenetic variation in isogenic mice. The associations of SHBG with cardio-metabolic parameters remained significant in all subjects after controlling for maternal age and education, BMI, time of gestation, smoking, metabolic HOMA-IR, hepatic enzymes and serum lipids and endocrine parameters HMW adiponectin, free testosterone and estradiol in multiple regression analyses. Diabetol Metab Syndr. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Offspring of HFD-fed mothers had increased proportions of both mwternal body fat and abdominal fat, hyperinsulinemia on oral glucose tolerance test at 15 min and elevated liver triglyceride content. In human studies, maternal nutrition as early as conception, can modulate DNA methylation of important genes. DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial. Buckley et al. DNA methylation mediates genotype and smoking interaction in the development of anti-citrullinated peptide antibody-positive rheumatoid arthritis.

Introduction

The effects of high-fat diet exposure in utero on the obesogenic ogfspring diabetogenic traits through epigenetic changes in adiponectin and leptin gene expression for multiple generations in female mice. Role of early hormonal and nutritional experiences in shaping feeding behavior and hypothalamic development. Changes in androgens and insulin sensitivity indexes throughout pregnancy in women with polycystic ovary syndrome PCOS : relationships with adverse outcomes. Influence of maternal obesity on the long-term health of offspring.

Pollock ; Carol A. The avenues for thw research will be discussed. Fatty acids and chronic low grade inflammation associated with obesity and the metabolic syndrome. We examined associations between maternal overweight and obesity severity and risk of cardiovascular diseases in young offspring. The mechanism of leptin resistance due to maternal obesity may be permanently programmed by intrauterine overnutrition as a result of alterations in neural circuitry that is similar to that induced by HFD consumption [ 90 ]. The effect of pre-existing maternal obesity and diabetes on placental mitochondrial content and electron transport chain activity. Maternal nutrition and risk of obesity in offspring: the Trojan horse of developmental plasticity.

Publication types Research Support, Non-U. Fetal programming of chronic kidney disease: the role of maternal smoking, mitochondrial dysfunction, and epigenetic modfification. Maternal obesity impairs brain glucose metabolism and neural response to hyperglycemia in male rat offspring. Background: The epidemic of overweight involves pregnant women. Search ADS. DNA methylation typically occurs at CpG dinucleotide sites regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide via the action of DNA methyltransferase enzymes.

Results: In neonates, maternal overweight, especially in the last trimester, predicted a thicker left ventricular posterior wall at birth 4. As all-important gatekeeper between the maternal and fetal circulations, the placenta is likely to play a critical offsppring in fetal programming as previously described. The prevalence and impact of overweight and obesity in an Australian obstetric population. Maternal obesity upregulates fatty acid and glucose transporters and increases expression of enzymes mediating fatty acid biosynthesis in fetal adipose tissue depots. For example, is early gestation most important when placental implantation is occurring or is late gestation more important when final kidney maturation is taking place? Placental glucose transport and GLUT 1 expression in insulin-dependent diabetes. However, the placental role in transferring glucose from mother to fetus is yet more complex where fetal hyperinsulinemia, in response to fetal hyperglycemia can steepen the glucose gradient, known as glucose steal [ 97 ].

Publication types

Effects of maternal obesity on fetal growth and body composition: implications for programming and future health. Maternal overnutrition impacts offspring adiposity and brain appetite markers-modulation by postweaning diet. A very powerful example of the potential effects of epigenetic modification comes from animal experiments involving the Agouti mouse. In contrast, if the agouti gene is unmethylated, the mouse is yellow-furred and obese with dysregulated metabolism. Maternal factor.

Pregnant obese dams have lower adiponectin levels and similarly offspring of obese mothers also have lower adiponectin levels [ 89 ]. Age at assessment, gender, maternal age at delivery, parity, maternal pre-pregnancy alcohol intake, household social class, birth weight. The known mechanisms of developmental programming on chronic disease risk in offspring are depicted in Figure 1. Table 3 Maternal anthropometric characteristics of dams at the time of weaning day 21 postpartum. All of them are up-regulated in the adipose tissue of offspring of obese mothers [ 84 ]. Castaneda-Gutierrez et al. Offspring of HFD-fed mothers had increased proportions of both total body fat and abdominal fat, hyperinsulinemia on oral glucose tolerance test at 15 min and elevated liver triglyceride content.

Specifically, epidemiological studies have shown that offspring born to obese hearg are at an increased risk of obesity, type 2 diabetes T2Dcardiovascular disease, and non-alcoholic fatty liver disease NAFLD Table 1. Male offspring from obese mothers showed significantly greater abdominal fat than control offspring although no significant difference in body weight between the groups was found. Because the long-term effects of maternal obesity could have profound public health implications, there is an urgent need for studies on causality, underlying mechanisms, and effective interventions to reverse the epidemic of obesity in women of childbearing age and to mitigate consequences for offspring. Comparator group. Maternal obesity and the developmental programming of hypertension: a role for leptin. Several human studies have shown that offspring born to diabetic mothers are at increased risk of hypertension, hyperfiltration, and CKD [ 39 ].

BiosciAbstracts

Crit Rev Clin Lab Sci. The odds ratios ORs for any adverse outcome were calculated for each gestational weight gain category within the particular clinical BMI group vs all other women within that BMI group. Waterland R. The ORs and ARRs for each gestational weight gain category used to determine the optimal ranges appear in eTable 8 and eTable 9 in the Supplementrespectively. Perinatal Practice.

Semin Reprod Med. Maternal overweight and obesity are associated with alterations in placental structure and function, characterized by increased inflammation and lipotoxic effects affecting nutrient transport, energy homeostasis, angiogenesis, and villous maturation [ 151819 ]. We conducted an individual participant data meta-analysis of data frommothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. Risks of overweight and abdominal obesity at age 16 years associated with prenatal exposures to maternal prepregnancy overweight and gestational diabetes mellitus. Similar results were observed when performing 2-stage random effects meta-analyses, with low to moderate heterogeneity S3 and S4 Figs. The role of miRNAs as biomarkers for pregnancy outcomes: a comprehensive review.

ALSO READ: Singapore Obesity Prevalence In The United

A maternal obesity and heart disease in the offspring torrent understanding of maternal risk factors holds the potential to improve both prenatal detection of CHD by identifying at-risk pregnancies, along with primary prevention of disease tprrent improving preconception and prenatal treatment of at-risk mothers. Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype. The outcome of increased oxidative stress and dysfunctional repair mechanisms is likely to be impaired placental function, which may thereby lead to unhealthy fetal growth and development. The placenta is now recognized as an integral programming agent for chronic disease in offspring and in particular, placental efficiency is a predictor of disease. Substances Biomarkers Blood Glucose. There is a complex interplay between epigenetic processes such that coupling between DNA methylation and histone modification increases the complexity of gene regulation.

Methods: Echocardiography was performed offapring infants born to lean and overweight mothers at birth and at 3, 6, and 12 months of age. Mitochondrial dysfunction has been demonstrated as early as embryogenesis by maternal obesity [ ]. Clinical implications. Maternal environment and the transgenerational cycle of obesity and diabetes. Gestational weight gain in relation to offspring body mass index and obesity from infancy through adulthood.

PubMed Google Scholar. SHBG is present in the fetal circulation and in cord blood [ 36 ]. Hsa-miRa-3p had respective values that were 2. Arterioscler Thromb Vasc Biol. Prev Next. Previous studies of dietary and physical activity interventions for pregnant women have not shown an effect on pregnancy outcomes.

Obesity during pregnancy

Considering maternal dietary modulators for epigenetic regulation and programming of the fetal epigenome. Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study. The study by Masuyama et al.

Identification of hub genes in colorectal cancer based on weighted gene co-expression network analysis. Many animal studies have utilized dietary manipulation in rodent models to examine the effects of maternal obesity on the offspring. Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 person years. This is due to the disruption in delivery of nutrients to the growing fetus that leads to intrauterine growth restriction, which has permanent deleterious effects on renal health in postnatal life [ 66 ]. Close Modal. Effect of birth weight on adulthood renal function: a bias adjusted meta-analytic approach.

At 6 months, offspring of obese mothers were heavier, with increased adiposity, endothelial obwsity, hypertensive, and significantly reduced skeletal muscle mass. There has been some suggestions that early life exposure to hyperleptinemia may contribute to establishing hypertension in the offspring of obese mothers [ 47 ]. Fasting insulin was raised at 3 months and by 6 months fasting glucose was elevated King et al. Maternal obesity and the developmental programming of hypertension: a role for leptin.

Glastras, Hui Chen, Carol A. The kidneys of offspring of obese compared with lean mothers examined at Day 20, Week 9 and through to Week 32 showed persistent evidence of inflammation, oxidative stress, and fibrosis. The appearance of mitochondrial defects preceded the onset of albuminuria at postnatal week Maternal obesity is associated with even greater increases in maternal lipid mobilization and triglyceride. Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice. Maternal obesity is known to modulate how the placenta forms and functions [ 93 ].

1. INTRODUCTION

Absolute risk reductions for the associations of gestational weight gain categories with any adverse outcome per maternal clinical body mass index group eTable Tofrent of inadequate and excessive gestational weight gain by classifications from this study and IOM with adverse maternal and infant outcomes, hospital-based population used as validation sample. The plan for analyses given to the cohorts when inviting them to participate in the MOCO collaboration is provided in S1 Text. The underlying mechanisms that trigger obesity-related epigenetic changes are still incompletely understood. J Obestet Gynaecol Can.

  • Insulin signaling plays an important role in placental growth and development that is supported by the observation of a higher trophoblastic insulin receptor expression in early gestation compared to late gestation [ 22 ].

  • Maternal obesity affects inflammatory and iron indices in umbilical cord blood.

  • Mamm Genome.

  • Increased maternal nutrition stimulates peroxisome proliferator activated receptor-gamma, adiponectin, and leptin messenger ribonucleic acid expression in adipose tissue before birth.

  • Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition.

As highlighted by a few existing and heart disease, potential future studies should employ combinations of genome-wide and epigenome-wide association studies, to better delineate what contribution the respective mechanism makes. Considering maternal dietary modulators for epigenetic regulation and programming of the fetal epigenome. Effects of an antenatal lifestyle intervention on offspring obesity—a 5-year follow-up of a randomized controlled trial. Information regarding optimal gestational weight gain across a range of maternal BMI categories is important for the identification of groups at increased risk. Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Among women categorized as normal weight, the absolute risk for any adverse outcome ranged from

The odds ratios for the hdart of any adverse outcome were 1. As the placenta is the main interface between mother and fetus, it is regulated by, both, torrsnt and maternal signals. In commonly used array approaches only maternal obesity and heart disease in the offspring torrent fraction of genomic CpGs are covered and measurement is to some degree biased toward the measurement of promoter methylation, neglecting other regions and functions of DNA methylation [ 727374 ]. Nat Rev Genet. Early excessive energy intake, together with maternal obesity, lead to altered DNA methylation within promoter regions of hypothalamic genes. The association between the methylation status and maternal obesity was studied using beta regression models with pregestational BMI as predictor and the methylation level of each CpG as response. Strengths and limitations We meta-analyzed original data of different pregnancy and birth cohorts, limiting the potential of publication bias and enabling a consistent definition of exposures and outcomes and adjustment for potential confounders.

Maternal obesity programs metabolic disease in offspring

J Physiol. The odds ratios for the risk of any adverse outcome were 1. Gestational weight gain in relation to offspring obesity over the life course: a systematic review and bias-adjusted meta-analysis. Nat Protoc.

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. Patel et al. Nephrogenesis is complete by 32—36 weeks in humans and thereafter no new nephrons are formed. Dosch et al. When pregnant yellow-furred Agouti mice are fed methyl-rich diet, they produce mostly healthy brown-furred offspring. Fetal exposure to maternal type 1 diabetes is associated with renal dysfunction at adult age.

When the agouti gene is in its normal methylated state, the coat is brown and the mouse has low risk of metabolic disease. In the context of premature delivery or intrauterine growth restriction, nephron endowment is reduced and thus the normal physiological dissase becomes overwhelmed leading to hyperfiltration and subsequent glomerular hypertrophy which may ultimately lead to CKD and systemic and intraglomerular hypertension [ 497576 ]. Abbreviation: HFD, high-fat diet. How does severity of maternal overweight and obesity impact rates of complex and specific heart defects in offspring? Interestingly, postnatal feeding of HFD in offspring augmented the deleterious renal effects of maternal obesity, confirming the negative impact of persistent high calorie diet. Sinceglobal obesity has doubled, and the incidence of cardiometabolic diseases such as type 2 diabetes and heart disease is also increasing. Level of evidence.

Publications

Maternal pregnancy information was selected strictly from medical records. Data on gestational weight gain kgdefined as the difference between the latest weight before delivery and pre-pregnancy weight, was provided by the cohorts, and was categorized as inadequate, adequate, or excessive weight gain in relation to maternal pre-pregnancy BMI according to the guidelines of the US Institute of Medicine IOM [ 11 ]. Ding designed and supervised the project, and provided final approval of the manuscript.

Get Permissions. Maternal obesity is known to modulate anr the placenta forms and functions [ 93 ]. Utilizing rodent models of maternal obesity, research within our laboratory has established that maternal obesity is a significant risk factor for the future development of CKD in offspring. Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition. Skip Nav Destination Article Navigation. Maternal obesity affects inflammatory and iron indices in umbilical cord blood. Forsen et al.

Am J Epidemiol. Among qnd categorized as overweight, the absolute risk for any adverse outcome increased from Associations of categories of gestational weight gain in first half of pregnancy with any adverse outcome per maternal clinical body mass index group eFigure 7. It maps to chromosome 19q Consequently, obesity-related prepregnancy insulin resistance is associated with a strongly increased risk for GDM [ 1 ].

Study Questions:

Utilizing rodent models of maternal obesity, research within our laboratory has established that maternal obesity is a significant risk factor for the future development of CKD in offspring. Altered body composition and metabolism in the male offspring of high fat-fed rats. Influencing factors and cellular mechanisms leading to the development of CKD in offspring.

  • Optimal Gestational Weight Gain. Developmental origins of disease and determinants of chromatin structure: Maternal diet modifies the primate fetal epigenome.

  • Our previous studies established association with respect to maternal obesity and renal effects in offspring, however were not able to demonstrate direct causality.

  • Competing interests: The authors have declared that no competing interests exist. My recently viewed abstracts.

  • Keywords: Epigenetics; gestational diabetes; maternal obesity; mitochondria; type 2 diabetes.

  • In humans, nephron endowment, defined as the number of nephrons at the start of postnatal life, is an important determinant of adult kidney health [ 75 ]. At 6 months: no additional effect of maternal overnutrition was seen.

They are primate-specific and comprise 46 miRNA genes [ 29 ]. The symbols represent the absolute risk for women in each gestational weight gain category. In the study by Waterland et al. For the prevention of childhood overweight and obesity, insight into the combined effects of maternal BMI and gestational weight gain is important.

What do these findings mean? Compared to lean women, obese woman display an increased lipid accumulation in the placenta, which can ultimately affect the placental lipid supply to the fetus and therefore might be a cause for increased fetal adiposity in offspring of obese women [ 21obezity26 ]. The current article gives an overview of pathophysiological changes associated with maternal obesity and their consequences on placental structure and function. Interpretation of main findings Maternal obesity does not only affect pregnancy outcomes, but may also have persistent effects on offspring fat development. Epigenetic modifications, like DNA methylation and histone modification, play key roles in biological activities. We suggest that SHBG could represent an integrating biomarker for an adverse cardio-metabolic profile in pregnant women with pregestational plus gestational obesity. Commonly, DNA methylation of leukocyte DNA is evaluated as surrogate parameter for epigenetic changes in the whole organism.

Abstract Objectives: The aim of this study was to investigate the consequences of maternal overweight on cardiac development in offspring trrent infants short term and minipigs short and longer term. Age at assessment, gender, maternal age at delivery, parity, maternal pre-pregnancy alcohol intake, household social class, birth weight. Cross-talk amongst adipose tissue, placenta, and fetal kidney development in maternal obesity. Gov't Review.

Global, regional, and national prevalence of overweight and obesity in children and adults during A systematic analysis for the Global Burden of Disease Study horrent They were able to show a partial but significant overlap of genes that experienced an increase in DNA methylation and a reciprocal decrease in DNA hydroxymethylation with increased maternal obesity, suggesting a possible decrease in the conversion efficiency of methylation to hydroxymethylation, which is governed by TET dioxygenases Fig. The fact that epigenetic mechanisms e.

In fact, maternal obesity and diabetes during pregnancy, which are on the rise, are strongly associated with altered fetal growth and development as well as with lifelong perturbations in metabolic tissues. Specifically, epidemiological studies have shown that offspring born to obese mothers are at an increased risk of obesity, type 2 diabetes T2Dcardiovascular disease, and non-alcoholic fatty liver disease NAFLD Table 1. McCurdy et al. Glastras, Hui Chen, Carol A. Abstract Background: Maternal overweight and obesity might increase risks of adiposity and cardiovascular and metabolic diseases in offspring.

ALSO READ: Morbidly Obese And Pregnant Debate Team Names

An imbalance between reactive oxygen species and antioxidant defense mechanisms leads to cellular damage matetnal oxidative stress. HFD-fed offspring of HFD-fed mothers had increased body weight, fat mass, and glucose intolerance with increased insulin, leptin, insulin resistance, and hyperphagia compared with offspring tirrent chow-fed mothers. In a series of elegantly designed experiments taking place in a remote community in the Gambia, maternal nutritional status at the time of conception was shown to alter methylation status of a host of genes in the cord blood of offspring [ — ]. However, diet-induced HFD-feeding in offspring remained a very powerful means of inducing weight gain, glucose intolerance, albuminuria, and renal damage, which overpowers the effect of maternal obesity by postnatal week 32 [ 46 ]. Multiple roles of haem in cystathionine b-synthase activity: implications for hemin and other therapies of acute hepatic porphyria. The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet.

Consequently, obesity-related prepregnancy insulin resistance is associated with a strongly increased risk for GDM [ 1 ]. Author summary Why was this study done? Received : 20 February Physiological Rev.

Genomic features are shown as custom tracks in the UCSC genome browser. Information regarding optimal gestational weight gain across a range of maternal BMI categories is important for the identification of groups at increased risk. Camilla S.

  • These associations were not explained by gestational diabetes or gestational hypertensive disorders S3 and S4 Tables. Adverse Maternal and Infant Outcomes.

  • In a study of overweight and obese Spanish women, reduced placental expression of mammalian target of rapamycin and up-regulation of sirtuin 1 and uncoupled protein 2 were demonstrated. At 6 months: no additional effect of maternal overnutrition was seen.

  • Both may, at least partly, be explained by intra-uterine programming mechanisms.

  • The ORs for the risk of any adverse outcome were 1.

  • Maternal and infant diagnoses were obtained from national registries.

Perinatal Practice. Ma, Academic Editor. KEGG pathway analysis of target genes was classified into six terms, including cellular processes, environmental information procession, genetic information procession, human diseases, metabolism and organismal systems, and showed these genes mainly participated in endocrine, immune, digestive and nervous systems Fig. Placental microRNA expression is not altered by maternal obesity and fetal overgrowth.

Voerman E. Early Hum. Maternal obesity is associated with altered expression of some epigenetic regulators in the fetal liver and upregulation in the transcript levels of some methyltransferase enzymes [ 58 ]. Dolinoy D. Results of the study revealed an association between maternal BMI and cord blood DNA methylation variation at sites that was strongly reduced to CpG sites after adjusting for estimated cell proportions. Maternal obesity and prenatal programming. Consequently, the methylation status can influence the expression of a metastable epiallele.

Absolute risk reductions for the associations of gestational weight gain categories with any adverse outcome per maternal clinical body mass index maternal obesity and heart disease in the offspring torrent eTable The highest absolute matednal were The maternal high-fat feeding modulated hepatic miRNA expression miRp, miRp, miRb, and miRb were down-regulated, whereas miR was up-regulated in offspring livers and increased body weight and impaired glucose metabolism at weaning. Maternal pre-pregnancy BMI and, to a smaller extent, gestational weight gain are important modifiable risk factors of childhood weight status with a considerable population impact. Poston L. Third, data on prepregnancy weight was mainly self-reported, and the latest weight during pregnancy was either self-reported or measured.

An imbalance between reactive oxygen species and antioxidant defense mechanisms leads to cellular damage via oxidative stress. Reduced nephron endowment in the neonates of Indigenous Australian peoples. The role of epigenetics in modulating the effects of maternal obesity on metabolic disease in offspring is an important area for future research and no doubt will provide explanation for the transgenerational propagation of metabolic disease. Second, a randomized, controlled trial where Gambian women were given micronutrient supplementation, determined that particular candidate genes had altered methylation status as a result of the supplement as measured in cord blood of offspring [ ].

Of all children, 6. Methods of calculating deaths attributable to obesity. Quiz Ref ID The observed results were similar after adjustment for gestational age at birth and after excluding preterm births. MiRNAs are small non-coding RNA molecules which function in post-transcriptional regulation of gene expression [ 85 ].

It does not intend to provide an exhaustive list of all studies completed on the topic. Fatty acid synthase and multiple fatty offsprinng transporters have been shown to be up-regulated in retroperitoneal, omental, mesenteric, and subcutaneous fat deposits. An objective for future studies is to determine the role of the placenta in orchestrating the effect of perturbations related to maternal obesity on metabolic programming within the fetal kidney. In a study of overweight and obese Spanish women, reduced placental expression of mammalian target of rapamycin and up-regulation of sirtuin 1 and uncoupled protein 2 were demonstrated. This is due to the disruption in delivery of nutrients to the growing fetus that leads to intrauterine growth restriction, which has permanent deleterious effects on renal health in postnatal life [ 66 ].

Similarly, the absolute risks were estimated for any adverse outcome and for each individual outcome across the range of gestational weight gain categories within each clinical BMI group. Effects of an antenatal lifestyle intervention on offspring obesity—a 5-year follow-up of a randomized controlled trial. BMJ Open. All serum samples for assessment of soluble SHBG and metabolic markers were obtained under fasting conditions at second trimester of pregnancy between 24 and 28 gestation weeksat the time of assessment of glucose tolerance. Inclusion Criteria and Participating Cohorts.

Torrent, a large randomized, controlled trial carried out in the Gambian communities demonstrated the powerful effect of periconceptional maternal nutrition on DNA methylation in offspring blood and hair and was predicted by periconceptional maternal offspting concentrations of key micronutrients, such as homocysteine, folate, and B vitamins [ ]. The outcome of increased oxidative stress and dysfunctional repair mechanisms is likely to be impaired placental function, which may thereby lead to unhealthy fetal growth and development. GB Impact of maternal obesity on offspring obesity and cardiometabolic disease risk. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. DNA methylation is usually associated with down-regulation or silencing of gene expression via direct methylation at non-CpG sites.

These changes can impact the eating behavior and maintenance of body weight [ 77 ]. The placenta is a major production site for pregnancy-related hormones that are released into the maternal circulation eliciting important functions in the adaptation of the maternal organism to and in the maintenance of pregnancy [ 16 ]. Murabayashi N. Adiposity is significantly associated with sex hormones, and adipose tissue contributes to the production of sex hormones in women [ 56 ].

Predicted target genes of these five C19MC miRNAs showed their obsity in signaling pathways which contribute to the control of newborn development, such maternal obesity and heart disease in the offspring torrent the nervous system, post-embryonic development and lipid and glucose homeostasis signaling pathways. Data on gestational weight gain kgdefined as the difference between the latest weight before delivery and pre-pregnancy weight, was provided by the cohorts, and was categorized as inadequate, adequate, or excessive weight gain in relation to maternal pre-pregnancy BMI according to the guidelines of the US Institute of Medicine IOM [ 11 ]. In utero exposure to a high-fat diet programs hepatic hypermethylation and gene dysregulation and development of metabolic syndrome in male mice. The authors read and approved the final manuscript.

Read more about:

Sidebar1?
Sidebar2?