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Current Diabetes Reports Nov 2019This review will focus on the long-term outcomes in offspring exposed to in utero hyperglycemia and gestational diabetes (GDM), including obesity, adiposity, glucose... (Review)
Review
PURPOSE OF REVIEW
This review will focus on the long-term outcomes in offspring exposed to in utero hyperglycemia and gestational diabetes (GDM), including obesity, adiposity, glucose metabolism, hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and puberty.
RECENT FINDINGS
There is evidence, mostly from observational studies, that offspring of GDM mothers have increased risk of obesity, increased adiposity, disorders of glucose metabolism (insulin resistance and type 2 diabetes), and hypertension. In contrast, evidence from the two intervention studies of treatment of mild GDM and childhood measures of BMI, adiposity, and glucose tolerance do not demonstrate that GDM treatment significantly reduces adverse childhood metabolic outcomes. Thus, more evidence is needed to understand the impact of maternal GDM on offspring's adiposity, glucose metabolism, lipid metabolism, risk of fatty liver disease, and pubertal onset. Offspring of GDM mothers may have increased risk for metabolic and cardiovascular complications. Targeting this group for intervention studies to prevent obesity and disorders of glucose metabolism is one potential strategy to prevent adverse metabolic health outcomes.
Topics: Adiposity; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Hyperglycemia; Hypertension; Insulin Resistance; Metabolic Diseases; Obesity; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 31754898
DOI: 10.1007/s11892-019-1267-6 -
European Journal of Clinical Nutrition Dec 2021Over the last few decades, the prevalence of obesity has risen to epidemic proportions worldwide. Consequently, the number of obesity in pregnancy has risen drastically.... (Review)
Review
Over the last few decades, the prevalence of obesity has risen to epidemic proportions worldwide. Consequently, the number of obesity in pregnancy has risen drastically. Gestational overweight and obesity are associated with impaired outcomes for mother and child. Furthermore, studies show that maternal obesity can lead to long-term consequences in the offspring, increasing the risk for obesity and cardiometabolic disease in later life. In addition to genetic mechanisms, mounting evidence demonstrates the induction of epigenetic alterations by maternal obesity, which can affect the offspring's phenotype, thereby influencing the later risk of obesity and cardiometabolic disease. Clear evidence in this regard comes from various animal models of maternal obesity. Evidence derived from clinical studies remains limited. The current article gives an overview of pathophysiological changes associated with maternal obesity and their consequences on placental structure and function. Furthermore, a short excurse is given on epigenetic mechanisms and emerging data regarding a putative interaction between metabolism and epigenetics. Finally, a summary of important findings of animal and clinical studies investigating maternal obesity-related epigenetic effects is presented also addressing current limitations of clinical studies.
Topics: Animals; Epigenesis, Genetic; Female; Humans; Obesity; Obesity, Maternal; Overweight; Placenta; Pregnancy
PubMed: 34230629
DOI: 10.1038/s41430-021-00905-6 -
Frontiers in Neuroscience 2022A maternal high-fat diet affects offspring neurodevelopment with long-term consequences on their brain health and behavior. During the past three decades, obesity has... (Review)
Review
A maternal high-fat diet affects offspring neurodevelopment with long-term consequences on their brain health and behavior. During the past three decades, obesity has rapidly increased in the whole human population worldwide, including women of reproductive age. It is known that maternal obesity caused by a high-fat diet may lead to neurodevelopmental disorders in their offspring, such as autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, and schizophrenia. A maternal high-fat diet can affect offspring neurodevelopment due to inflammatory activation of the maternal gut, adipose tissue, and placenta, mirrored by increased levels of pro-inflammatory cytokines in both maternal and fetal circulation. Furthermore, a maternal high fat diet causes gut microbial dysbiosis further contributing to increased inflammatory milieu during pregnancy and lactation, thus disturbing both prenatal and postnatal neurodevelopment of the offspring. In addition, global molecular and cellular changes in the offspring's brain may occur due to epigenetic modifications including the downregulation of brain-derived neurotrophic factor (BDNF) expression and the activation of the endocannabinoid system. These neurodevelopmental aberrations are reflected in behavioral deficits observed in animals, corresponding to behavioral phenotypes of certain neurodevelopmental disorders in humans. Here we reviewed recent findings from rodent models and from human studies to reveal potential mechanisms by which a maternal high-fat diet interferes with the neurodevelopment of the offspring.
PubMed: 35937892
DOI: 10.3389/fnins.2022.909762 -
Genes Feb 2023The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to... (Review)
Review
The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 years of age have an increased risk of infertility, pregnancy problems, spontaneous abortion, congenital malformations, and postnatal issues. There are varying opinions on whether a father's age affects the quality of his sperm or his ability to father a child. First, there is no single accepted definition of old age in a father. Second, much research has reported contradictory findings in the literature, particularly concerning the most frequently examined criteria. Increasing evidence suggests that the father's age contributes to his offspring's higher vulnerability to inheritable diseases. Our comprehensive literature evaluation shows a direct correlation between paternal age and decreased sperm quality and testicular function. Genetic abnormalities, such as DNA mutations and chromosomal aneuploidies, and epigenetic modifications, such as the silencing of essential genes, have all been linked to the father's advancing years. Paternal age has been shown to affect reproductive and fertility outcomes, such as the success rate of in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and premature birth rate. Several diseases, including autism, schizophrenia, bipolar disorders, and paediatric leukaemia, have been linked to the father's advanced years. Therefore, informing infertile couples of the alarming correlations between older fathers and a rise in their offspring's diseases is crucial, so that they can be effectively guided through their reproductive years.
Topics: Pregnancy; Humans; Male; Female; Child; Paternal Age; Semen; Fertility; Reproduction; Fathers; Infertility
PubMed: 36833413
DOI: 10.3390/genes14020486 -
Frontiers in Cellular and Infection... 2022The prevalence of obesity is increasingly common in the United States, with ~25% of women of reproductive age being overweight or obese. Metaflammation, a chronic low... (Review)
Review
The prevalence of obesity is increasingly common in the United States, with ~25% of women of reproductive age being overweight or obese. Metaflammation, a chronic low grade inflammatory state caused by altered metabolism, is often present in pregnancies complicated by obesity. As a result, the fetuses of mothers who are obese are exposed to an in-utero environment that has altered nutrients and cytokines. Notably, both human and preclinical studies have shown that children born to mothers with obesity have higher risks of developing chronic illnesses affecting various organ systems. In this review, the authors sought to present the role of cytokines and inflammation during healthy pregnancy and determine how maternal obesity changes the inflammatory landscape of the mother, leading to fetal reprogramming. Next, the negative long-term impact on offspring's health in numerous disease contexts, including offspring's risk of developing neuropsychiatric disorders (autism, attention deficit and hyperactive disorder), metabolic diseases (obesity, type 2 diabetes), atopy, and malignancies will be discussed along with the potential of altered immune/inflammatory status in offspring as a contributor of these diseases. Finally, the authors will list critical knowledge gaps in the field of developmental programming of health and diseases in the context of offspring of mothers with obesity, particularly the understudied role of hematopoietic stem and progenitor cells.
Topics: Child; Cytokines; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Obesity; Obesity, Maternal; Pregnancy
PubMed: 36189369
DOI: 10.3389/fcimb.2022.940937 -
Microbiome May 2023The Western dietary pattern, characterized by high consumption of fats and sugars, has been strongly associated with an increased risk of developing Crohn's disease...
BACKGROUND
The Western dietary pattern, characterized by high consumption of fats and sugars, has been strongly associated with an increased risk of developing Crohn's disease (CD). However, the potential impact of maternal obesity or prenatal exposure to a Western diet on offspring's susceptibility to CD remains unclear. Herein, we investigated the effects and underlying mechanisms of a maternal high-fat/high-sugar Western-style diet (WD) on offspring's susceptibility to 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced Crohn's-like colitis.
METHODS
Maternal dams were fed either a WD or a normal control diet (ND) for eight weeks prior to mating and continued throughout gestation and lactation. Post-weaning, the offspring were subjected to WD and ND to create four groups: ND-born offspring fed a normal diet (N-N) or Western diet (N-W), and WD-born offspring fed a normal (W-N) or Western diet (W-W). At eight weeks of age, they were administered TNBS to induce a CD model.
RESULTS
Our findings revealed that the W-N group exhibited more severe intestinal inflammation than the N-N group, as demonstrated by a lower survival rate, increased weight loss, and a shorter colon length. The W-N group displayed a significant increase in Bacteroidetes, which was accompanied by an accumulation of deoxycholic acid (DCA). Further experimentation confirmed an increased generation of DCA in mice colonized with gut microbes from the W-N group. Moreover, DCA administration aggravated TNBS-induced colitis by promoting Gasdermin D (GSDMD)-mediated pyroptosis and IL-1beta (IL-1β) production in macrophages. Importantly, the deletion of GSDMD effectively restrains the effect of DCA on TNBS-induced colitis.
CONCLUSIONS
Our study demonstrates that a maternal Western-style diet can alter gut microbiota composition and bile acid metabolism in mouse offspring, leading to an increased susceptibility to CD-like colitis. These findings highlight the importance of understanding the long-term consequences of maternal diet on offspring health and may have implications for the prevention and management of Crohn's disease. Video Abstract.
Topics: Humans; Pregnancy; Female; Mice; Animals; Crohn Disease; Diet, Western; Prenatal Exposure Delayed Effects; Colitis; Diet, High-Fat; Deoxycholic Acid; Mice, Inbred C57BL
PubMed: 37131223
DOI: 10.1186/s40168-023-01546-6 -
Current Treatment Options in Allergy 2018The aim of this paper is to review and summarize the current knowledge of prevention of airway allergy. (Review)
Review
PURPOSE OF REVIEW
The aim of this paper is to review and summarize the current knowledge of prevention of airway allergy.
RECENT FINDINGS
Allergic rhinitis and asthma are allergic airway diseases. Due to their increasing incidence and socioeconomic burden, allergic airway diseases have recently gained attention worldwide. The primary prevention of allergic airway diseases focuses on offspring's gestational and childhood environment, such as maternal smoking and diet during pregnancy and breastfeeding as well as exposure to environmental microbes and irritants.
SUMMARY
Asthma and allergic rhinitis are a major public health problem worldwide. They have increasing prevalence and thus attempts to their prevention are mandatory. Rapid action needs to be taken to restrain smoking among children and adolescents in order to prevent burden of allergic airway diseases. Exposure to pollution and environmental issues concerning hygiene and lifestyle would also need to be actively addressed. More evidence is still needed in order to draw linings concerning maternal diet and other factors during the offspring's whole life span.
PubMed: 30524932
DOI: 10.1007/s40521-018-0190-4 -
Paediatric and Perinatal Epidemiology Mar 2022Maternal overnutrition during pregnancy predisposes the offspring to cardiometabolic diseases. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Maternal overnutrition during pregnancy predisposes the offspring to cardiometabolic diseases.
OBJECTIVES
This systematic review and meta-analysis aimed to investigate the association between maternal overnutrition and offspring's blood pressure (BP) and the effect of offspring's obesity on this association.
DATA SOURCES
PubMed, EMBASE, Clinicaltrials.gov, CENTRAL.
STUDY SELECTION AND DATA EXTRACTION
Human studies published in English before October 2021 were identified that presented quantitative estimates of association between maternal overnutrition just before or during pregnancy and the offspring's BP.
SYNTHESIS
Random-effect model with the DerSimonian and Laird weighting method was used to analyse regression coefficients or mean differences.
RESULTS
After selection, 17 observational studies (140,517 mother-offspring pairs) were included. Prepregnancy body mass index (ppBMI) showed positive correlation with BP in offspring (regression coefficient for systolic: 0.38 mmHg per kg/m , 95% confidence interval (CI) 0.17, 0.58; diastolic: 0.10 mmHg per kg/m , 95% CI 0.05, 0.14). These indicate 1.9 mmHg increase in systolic and 0.5 mmHg increase in diastolic BP of offspring with every 5 kg/m gain in maternal ppBMI. Results on coefficients adjusted for offspring's BMI also showed association (systolic: 0.08 mmHg per kg/m , 95% CI 0.04, 0.11; diastolic: 0.03 mmHg per kg/m , 95% CI 0.01, 0.04). Independent from ppBMI, gestational weight gain (GWG) showed positive correlation with systolic BP (systolic BP: 0.05 mmHg per kg, 95% CI 0.01, 0.09), but not after adjustment for offspring's BMI. Mean systolic BP was higher in children of mothers with excessive GWG than in those of mothers with optimal GWG (difference: 0.65 mmHg, 95% CI 0.25, 1.05).
CONCLUSIONS
Independent from offspring's BMI, higher prepregnancy BMI may increase the risk for hypertension in offspring. The positive association between GWG and offspring's systolic BP is indirect via offspring's obesity. Reduction in maternal obesity and treatment of obesity in children of obese mothers are needed to prevent hypertension.
Topics: Blood Pressure; Body Mass Index; Child; Female; Gestational Weight Gain; Humans; Hypertension; Pediatric Obesity; Pregnancy
PubMed: 35041216
DOI: 10.1111/ppe.12859 -
Neuroscience and Biobehavioral Reviews Oct 2023Abnormal gestational weight gain (GWG) has been increasing globally, up to 47% of all pregnancies. Multiple studies have focused on the association between GWG and... (Meta-Analysis)
Meta-Analysis Review
Abnormal gestational weight gain (GWG) has been increasing globally, up to 47% of all pregnancies. Multiple studies have focused on the association between GWG and adverse neurodevelopmental outcomes in the offspring, however with inconsistent results. We performed a systematic review and meta-analysis to evaluate associations between excessive or insufficient GWG and offspring's neurodevelopmental outcomes. Meta-analysis of these 23 studies using a random-effects model revealed associations between excessive GWG and neurodevelopmental disorders (ASD & ID & ADHD together: OR=1.12 [95% CI 1.06-1.19]), ASD (OR=1.18 [95% CI 1.08-1.29]), ADHD (OR=1.08 [95% CI 1.02-1.14]), ASD with ID (OR=1.15 [95% CI 1.01-1.32]), and ASD without ID (OR=1.12 [95% CI 1.06-1.19]). Insufficient GWG was associated with higher risk for ID (OR=1.14 [95% CI 1.03-1.26]). These results emphasize the significant impact, though of small effect size, of GWG across multiple neurodevelopmental disorders. It is important to note that these results do not establish causality. Other factors such as genetic factors, gene-environment interactions may confound the relationship between GWG and neurodevelopmental outcomes. To better understand the role of GWG in neurodevelopmental disorders, future studies should consider using genetically sensitive designs that can account for these potential confounders.
Topics: Pregnancy; Female; Humans; Gestational Weight Gain; Weight Gain; Neurodevelopmental Disorders; Body Mass Index
PubMed: 37573899
DOI: 10.1016/j.neubiorev.2023.105360 -
Current Molecular Biology Reports 2017The prevalence of obesity has increased substantially in the current generations of Western countries, and the burden of obesity-related complications has been growing... (Review)
Review
PURPOSE OF REVIEW
The prevalence of obesity has increased substantially in the current generations of Western countries, and the burden of obesity-related complications has been growing steadily. In men, obesity is not only a major risk factor for serious chronic diseases, concern is growing that the reproductive capacity, and more particularly, their offspring's health may be affected. Obesity-related impaired spermatogenesis is associated with a decrease in microscopic and molecular sperm characteristics and pregnancy success. We hypothesize that epigenetics is an important mediator explaining interactions between an obesogenic environment and sperm/offspring outcomes.
RECENT FINDINGS
Recent studies have explored inter- and transgenerational epigenetic effects in sperm cells and in offspring. Father-to-child effects have been reported in relation to preconceptional nutritional and life-style related factors.
SUMMARY
Here, we summarize the current understanding about obesity and molecular or epigenetic underlying mechanisms in sperm. We identify the obesogenic environment of the father before conception as a potential origin of health or disease in the offspring and include it as part of a new concept, the (POHaD).
PubMed: 29387521
DOI: 10.1007/s40610-017-0083-5