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Cardiometabolic diseases are among the leading causes of morbidity and mortality worldwide and are influenced not only by genetic and environmental factors during adulthood but also by exposures occurring during intrauterine life. In this context, the Developmental Origins of Health and Disease (DOHaD) theory highlights the importance of fetal programming in determining future disease risk. This study aimed to analyze the role of epigenetic alterations in fetal programming and their relationship with the development of cardiometabolic diseases throughout life. An integrative literature review was conducted following the PRISMA 2020 guidelines. Searches were performed in PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Virtual Health Library using descriptors related to fetal programming, epigenetics, and cardiometabolic diseases. Articles published between 2020 and 2026 in English, Portuguese, and Spanish were included, resulting in a final sample of 17 studies after applying the eligibility criteria. The findings demonstrated that gestational factors such as maternal obesity, gestational diabetes, intrauterine growth restriction, and inadequate dietary patterns can induce persistent epigenetic modifications, including DNA methylation, histone alterations, and regulation by non-coding RNAs. These changes influence fetal gene expression and are associated with an increased risk of obesity, insulin resistance, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular diseases in the offspring. Furthermore, the placenta was found to play a significant role in mediating maternal inflammatory and metabolic effects on fetal development. It is concluded that epigenetic mechanisms constitute a fundamental link between adverse gestational exposures and the future development of cardiometabolic diseases, highlighting the importance of preventive strategies focused on maternal health before and during pregnancy, as well as the need for further research to deepen the understanding of fetal programming processes.
Referências
ALBA-LINARES, Juan José et al. Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways. Cardiovascular Diabetology, London, v. 22, n. 44, 2023. DOI: 10.1186/s12933-023-01774-y. Available at: https://doi.org/10.1186/s12933-023-01774-y. Accessed on: 8 ago. 2026.
BURDEN, Samuel J. et al. Maternal obesity and offspring cardiovascular remodelling: the effect of preconception and antenatal lifestyle interventions: a systematic review. International Journal of Obesity, London, 2024. DOI: 10.1038/s41366-024-01536-0.
CARLBERG, Carsten. Nutrition and epigenetic programming. Current Opinion in Clinical Nutrition and Metabolic Care, Philadelphia, v. 26, n. 2, p. 105-111, 2023. DOI: 10.1097/MCO.00000000000000900. Available at: https://doi.org/10.1097/MCO.0000000000000900. Accessed on: 8 ago. 2026.
ELGAZZAZ, Mona et al. Maternal Western diet programs cardiometabolic dysfunction and hypothalamic inflammation via epigenetic mechanisms predominantly in the male offspring. Molecular Metabolism, v. 79, 2024. DOI: 10.1016/j.molmet.2023.101864. Available at: https://doi.org/10.1016/j.molmet.2023.101864. Accessed on: 8 ago. 2026.
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HARARY, David; AKINYEMI, Ayodele; CHARRON, Maureen J. Fetal growth and intrauterine epigenetic programming of obesity and cardiometabolic disease. NeoReviews, Itasca, v. 23, n. 6, p. e363-e375, 2022. DOI: 10.1542/neo.23-6-e363. Available at: https://doi.org/10.1542/neo.23-6-e363. Accessed on: 8 ago. 2026.
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SCHEIDL, Taylor B.; BRIGHTWELL, Amy L.; EASSON, Sarah H.; THOMPSON, Jennifer A. Maternal obesity and programming of metabolic syndrome in the offspring: searching for mechanisms in the adipocyte progenitor pool. BMC Medicine, London, v. 21, n. 50, 2023. DOI: 10.1186/s12916-023-02730-z. Available at: https://doi.org/10.1186/s12916-023-02730-z. Accessed on: 8 ago. 2026.
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Copyright (c) 2026 Isabela da Silva Vieira, Emily Amaral Gonçalves, Júlia Sander Santos, Danieli Gomes Giacomin, Laura Nascimento Freitas, Mariana Costa dos Santos, Ana Luiza Latini Girolamy Daflon, Claudete Lúcia Carvalho Oliveira, Fernanda Mazzelli Almeida Maio