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February 20, 2026Cells0 citationsOpen Access

Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences

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GSGabriella SchieraGMGiulia MacajoneSVSara Volpes

Key Points

  • The review aims to explore the effects of maternal overnutrition on fetal programming and its long-term health consequences.
  • Analyzed existing literature on maternal nutrition's impact on offspring health.
  • Evaluated the role of gestational diabetes and obesity in fetal programming.
  • Investigated biochemical and epigenetic mechanisms influenced by maternal overnutrition.
  • Maternal overnutrition predisposes offspring to obesity and metabolic disorders in adulthood.
  • Cognitive dysfunction and immune alterations are linked to maternal obesity.
  • Gestational diabetes disrupts fetal appetite regulation and hypothalamic development.

Abstract

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.

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Cite This Study

Schiera et al. (2026) studied this question.

synapsesocial.com/papers/6997f9edad1d9b11b3452ce8https://doi.org/10.3390/cells15040366
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