דו״ח מאומת

Nutrition in pregnant mothers has long been known to be an important determinant of fetal/maternal outcomes. In general, the typical American diet shows opportunities for improvement. The intake of fruits, vegetables, whole grains, and fiber may be below recommended levels, but the relative proportion of sodium, fats, and carbohydrates seems high. In this review, we present current evidence on how the fetal/neonatal outcomes may be altered by maternal nutrition at the time of conception, fetal nutrition in utero, contribution of maternal dietary factors in fetal outcomes, weight gain during pregnancy, diabetes during pregnancy, fetal growth restriction (FGR), maternal nutritional status during later pregnancy, and pregnancy in adolescent mothers.…

PMID: 35659089

Herein, we present a thorough examination of the impact of maternal nutrition on fetal and infant neurodevelopment, focusing on specific nutrients and their critical roles in perinatal and pediatric health. Through a comprehensive narrative review of the literature, this study highlights the importance of a balanced maternal diet rich in nutrients like eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), folic acid, iron, and iodine in shaping children's neurological functions. Key findings underscore the influence of maternal nutrition during pregnancy and the peri-gestational period on children's cognitive, motor, speech, and socio-emotional development. Deficiencies in essential nutrients, such as DHA, are linked to adverse long-lasting outcomes such as premature birth and intrauterine growth restriction, where a suitable intake of iron and folic acid is vital to prevent neural tube defects and promote healthy brain development. We highlight areas requiring further investigation, particularly regarding iodine's impact and the risks associated with alcohol consumption during pregnancy. In conclusion, this research sheds light on our current understanding of maternal nutrition and child neurodevelopment, offering valuable insights for health professionals and researchers.…

PMID: 38823254

Over recent decades, a substantial body of research has expanded our understanding of how early-life conditions influence long-term health. These observations led to the formulation of the Barker Hypothesis, which postulates that adverse nutritional exposures during fetal life can induce persistent physiological and metabolic adaptations, thereby increasing susceptibility to chronic diseases later in life. This narrative review aims to provide a comprehensive overview of current recommendations for adequate maternal nutrition during pregnancy, with particular emphasis on key nutrients and specific dietary patterns. In addition, the effects of maternal diet on placental function and fetal growth are examined. A literature search was conducted in the following electronic databases: MEDLINE (via PubMed), Scopus, Web of Science, Embase, and the Cochrane Library. Manuscripts published between 2005 and 2025 were considered. The impact of prenatal nutritional exposures on immune development, neurodevelopment, metabolic regulation, and gut microbiota is also discussed, highlighting how these mechanisms may contribute to an increased long-term risk of non-communicable diseases, including obesity, metabolic syndrome, and neuropsychiatric disorders. Maternal nutrition during pregnancy plays a crucial role in shaping infants' and children's health, particularly regarding the development of non-communicable diseases. Therefore, ensuring adequate nutritional intake during this critical period-both quantitatively and qualitatively-is essential to optimize health outcomes for the newborn and to promote long-term well-being throughout childhood and beyond.…

PMID: 42123976

Nutrition is the major intrauterine environmental factor that alters expression of the fetal genome and may have lifelong consequences. This phenomenon, termed "fetal programming," has led to the recent theory of "fetal origins of adult disease." Namely, alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, and metabolism of the offspring, thereby predisposing individuals to metabolic, endocrine, and cardiovascular diseases in adult life. Animal studies show that both maternal undernutrition and overnutrition reduce placental-fetal blood flows and stunt fetal growth. Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenesis factor) and polyamines (key regulators of DNA and protein synthesis) may provide a unified explanation for intrauterine growth retardation in response to the 2 extremes of nutritional problems with the same pregnancy outcome. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the impact of maternal nutrition on both fetal programming and genomic imprinting. Promoting optimal nutrition will not only ensure optimal fetal development, but will also reduce the risk of chronic diseases in adults.…

PMID: 15333699

The developmental origins of health and disease (DOHaD) framework highlights the importance of the intrauterine environment in shaping lifelong health outcomes. Maternal nutrition, toxic exposures, and epigenetic reprogramming are key factors influencing offspring susceptibility to obesity and cardiometabolic disorders. However, prior reviews have typically addressed nutrition and toxicants separately, limiting insights into their combined effects on the fetal epigenome. This review integrates current evidence on how maternal nutrition and toxicant exposures converge through epigenetic mechanisms to influence obesity risk, while outlining translational opportunities for mitigating intergenerational metabolic disease. A narrative review was conducted of studies published from 2000 to 2025, sourced from PubMed, Scopus, and Web of Science, supplemented by manual screening. Search terms included maternal nutrition, environmental toxicants, epigenetic mechanisms, and offspring obesity outcomes. Studies on animal models, human cohorts, and intervention trials were included, focusing on links between maternal exposures, epigenetic changes, and metabolic disease. Maternal dietary imbalances, such as deficiencies in one-carbon donors or excess caloric intake, cause persistent epigenetic changes on genes regulating adipogenesis and energy homeostasis, increasing offspring obesity risk. Prenatal exposure to environmental toxicants, including endocrine disruptors and heavy metals, amplifies these vulnerabilities by altering DNA methylation, histone modifications, and noncoding RNA networks. Combined nutritional deficits and toxicant exposures, particularly in low- and middle-income countries (LMICs), create a "dual burden" that intensifies epigenetic instability. Nutrients like methyl donors and antioxidants may mitigate toxicant-induced epimutations, offering potential for precision maternal nutrition interventions. Maternal nutrition and toxicant exposures interact through epigenetic mechanisms to program obesity and related diseases. Addressing these factors through precision nutrition, stricter environmental regulations, and early-life epigenetic biomarkers offers promising prevention strategies. Large, diverse, multi-generational cohorts and multi-omics approaches are needed to strengthen causal inference and inform equitable policies to break the intergenerational cycle of metabolic disease. This study explores how a mother’s diet and exposure to environmental pollutants during pregnancy can shape her child’s future risk of obesity and related diseases such as diabetes and heart disease. It explains that what happens in the womb can “program” a baby’s metabolism for life through changes in gene activity known as epigenetic modifications which are chemical tags that switch genes on or off without changing DNA. Poor maternal nutrition, whether from eating too much fat and sugar or lacking key vitamins like folate and B…

PMID: 41497887

<h4>Background</h4>Maternal nutrition can shape fetal epigenetic programming with long-term health effects. This study tested whether central and peripheral tissues differ in responsiveness to maternal methyl-donor supplementation.<h4>Methods</h4>C57BL/6 dams received either standard chow (control) or a methyl-donor-enriched diet during pregnancy. Offspring were allocated to three groups: i) control (mother and offspring on standard chow), ii) prenatal exposure (mother on methyl-donor diet during pregnancy, offspring on standard chow thereafter), and iii) combined exposure (mother on methyl-donor diet during pregnancy and lactation, offspring continued methyl-donor diet postnatally). Global DNA methylation was measured by ELISA in the brain and hypothalamus (n = 10) and in the liver, spleen, and heart (n = 5). Exploratory hypothalamic gene expression analysis compared the prenatal exposure group vs controls (n = 4).<h4>Results</h4>Prenatal supplementation was associated with increased global 5-methylcytosine levels in the brain and hypothalamus (both P < 0.01). In the hypothalamus, this elevation persisted irrespective of later diet, whereas peripheral organs displayed ongoing plasticity and responded strongly to postnatal exposure. Microarray analysis identified 36 differentially expressed hypothalamic transcripts, including genes previously linked to methylation-related pathways.<h4>Conclusion</h4>Maternal methyl-donor supplementation is associated with a stable hypothalamic methylation profile established during intrauterine life, while peripheral organs remain epigenetically adaptable. These findings reveal an organ-specific divergence in developmental programming, with exploratory gene expression suggesting functional consequences.…

PMID: 42213526

Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and child. Children of mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease and GDM when they themselves become pregnant, perpetuating a multigenerational increased risk of metabolic disease. The negative effect of GDM is exacerbated by maternal obesity, which induces a greater derangement of fetal adipogenesis and growth. Multiple factors, including genetic, epigenetic and metabolic, which interact with lifestyle factors and the environment, are likely to contribute to the development of GDM. Genetic factors are particularly important, with 30% of women with GDM having at least one parent with T2D. Fetal epigenetic modifications occur in response to maternal GDM, and may mediate both multi- and transgenerational risk. Changes to the maternal metabolome in GDM are primarily related to fatty acid oxidation, inflammation and insulin resistance. These might be effective early biomarkers allowing the identification of women at risk of GDM prior to the development of hyperglycaemia. The impact of the intra-uterine environment on the developing fetus, "developmental programming", has a multisystem effect, but its influence on adipogenesis is particularly important as it will determine baseline insulin sensitivity, and the response to future metabolic challenges. Identifying the critical window of metabolic development and developing effective interventions are key to our ability to improve population metabolic health.…

PMID: 38288471

Epigenetics generates a considerable interest in the field of research on complex traits, including obesity and diabetes. Recently, we reported a number of epipolymorphisms in the placental leptin and adiponectin genes associated with maternal hyperglycemia during pregnancy. Our results suggest that DNA methylation could partly explain the link between early exposure to a detrimental fetal environment and an increased risk to develop obesity and diabetes later in life. This brief report discusses the potential importance of adipokine epigenetic changes in fetal metabolic programming. Additionally, preliminary data showing similarities between methylation variations of different tissues and cell types will be presented along with the challenges and future perspectives of this emerging field of research.…

PMID: 23700551

Gestational diabetes mellitus (GDM), characterized by gestational hyperglycemia due to insufficient insulin response, poses significant risks to both maternal and offspring health. Fetal exposure to maternal hyperglycemia leads to short-term complications such as macrosomia and neonatal hypoglycemia and long-term risks including obesity, metabolic syndrome, cardiovascular dysfunction, and type 2 diabetes. The Developmental Origins of Health and Disease (DOHaD) theory explains how maternal hyperglycemia alters fetal programming, increasing susceptibility to metabolic disorders later in life. This review explores the intergenerational impact of GDM, linking maternal hyperglycemia to lifelong metabolic, cardiovascular, and neurodevelopmental risks via epigenetic and microbiome alterations. It integrates the most recent findings, contrasts diagnostic methods, and offers clinical strategies for early intervention and prevention. A comprehensive literature search was conducted in PubMed, Scopus, and ScienceDirect to identify relevant studies published between 1 January 2000 and 31 December 2024. The search included studies focusing on the metabolic and developmental consequences of GDM exposure in offspring, as well as potential mechanisms such as epigenetic alterations and gut microbiota dysbiosis. Studies examining preventive strategies and management approaches were also included. Maternal hyperglycemia leads to long-term metabolic changes in offspring, with epigenetic modifications and gut microbiota alterations playing key roles. GDM-exposed children face increased risks of obesity, glucose intolerance, and cardiovascular diseases. Early screening and monitoring are crucial for risk reduction. Understanding the intergenerational effects of GDM has important clinical implications for prenatal and postnatal care. Early detection, lifestyle interventions, and targeted postnatal surveillance are essential for reducing long-term health risks in offspring. These findings emphasize the importance of comprehensive maternal healthcare strategies to improve long-term outcomes for both mothers and their children.…

PMID: 40141785

Maternal nutrition during pregnancy critically influences fetal programming, shaping the offspring's lifelong health and disease susceptibility. Both undernutrition and overnutrition affect fetal metabolism, predisposing offspring to obesity and cardiometabolic disorders in adulthood. This review examines current evidence on how maternal nutrition, particularly overnutrition and its complications, such as gestational diabetes mellitus (GDM) and obesity, affects offspring health. It also explores the biochemical and epigenetic mechanisms underlying aberrant fetal programming induced by an unfavorable intrauterine environment. Excess nutrient exposure in utero alters fetal metabolic pathways by modifying the expression of key metabolic genes and nutrient sensors, increasing susceptibility to metabolic syndrome later in life. Maternal obesity has additionally been linked to cognitive dysfunction, immune alterations, and elevated cancer-related mortality in the offspring. GDM exposure disrupts fetal hypothalamic development, impairing appetite regulation. Emerging evidence suggests that epigenetic changes induced by maternal overnutrition may be transmitted across generations and that paternal obesity may also contribute to fetal metabolic programming. Although lifestyle interventions during pregnancy have been tested, they show limited long-term benefits, whereas pre-pregnancy BMI remains the strongest predictor of offspring obesity, emphasizing the critical role of preconception care and the prevention of overweight in women of reproductive age.…

PMID: 41744809