Early-Life Nutritional Determinants of Pediatric MASLD

Area of Science:

• Hepatology and Metabolic Disorders
• Pediatric Gastroenterology
• Developmental Nutrition

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread liver condition affecting both children and adults.
• Pediatric MASLD presents distinct features compared to adult forms, suggesting unique developmental pathways.
• Intrauterine and early-life factors are increasingly recognized as crucial in the pathogenesis of pediatric MASLD.

Purpose of the Study:

• To review and synthesize evidence on prenatal, postnatal, and early childhood nutritional exposures linked to pediatric MASLD.
• To emphasize the critical early-life windows for potential interventions against pediatric MASLD.
• To understand the multi-hit continuum contributing to MASLD development from in utero.

Main Methods:

• Narrative review of existing human cohort studies and mechanistic model systems.
• Synthesis of converging evidence on nutritional exposures and hepatic lipid accumulation.
• Focus on prenatal (maternal health, diet), postnatal (feeding practices), and early childhood (diet quality) factors.

Main Results:

• Maternal factors like obesity and gestational diabetes are associated with increased offspring hepatic steatosis.
• Postnatal feeding (breastfeeding vs. formula with added sugars) and early childhood diets influence MASLD susceptibility.
• Combined genetic and environmental factors contribute to the heterogeneity of pediatric MASLD.

Conclusions:

• Pediatric MASLD development is a complex continuum influenced by early-life exposures.
• Nutritional interventions during pregnancy and early childhood are vital for preventing MASLD.
• Targeting early-life windows offers a promising strategy to reduce the global burden of pediatric MASLD.