Maternal Thyroid Disorders and Their Effects on the Metabolic Profile of Breast Milk: A Systematic Review

Human breast milk composition is inextricably linked to maternal physiology, yet the impact of thyroid dysfunction on this biological matrix remains undercharacterized. Given that lactation serves as the primary metabolic conduit for the neonate, alterations in the milk metabolic profile could have profound developmental consequences. This study investigates metabolomic and proteomic differentiations in breast milk associated with maternal thyroid abnormalities to evaluate their potential implications for infant growth and neurodevelopment. A systematic search was conducted across PubMed, Embase, Web of Science, and Scopus to identify studies investigating the impact of maternal thyroid disorders on the metabolomic and proteomic composition of human breast milk. The Newcastle-Ottawa Scale was utilized to assess the risk of bias in the selected studies. The study was also registered in the International Prospective Register of Systematic Reviews (ID: CRD420261296307). Nine studies were included in the review. The most consistent finding was a significant alteration of the milk lipidome, characterized by an increase in saturated fatty acids and a depletion of neurocritical lipids, such as glycerophospholipids and nervonic acid. Hypothyroidism was associated with reduced total protein content and downregulation of membrane proteins, including adipophilin and butyrophilin. Additionally, thyroid dysfunction correlated with decreased levels of sialylated oligosaccharides. Conversely, specific immune modulators, such as the Ig gamma-3 chain, were upregulated. Although the primary complement system components remained unchanged, a significant increase was observed in CD59, an inhibitor of complement activation. Maternal thyroid dysfunction induces profound metabolomic and proteomic alterations in breast milk, fundamentally compromising its nutritional and structural integrity. The specific depletion of neurocritical lipids and immunomodulatory oligosaccharides, along with enzymatic downregulation, suggests a mechanism underlying impaired neurodevelopment, immune susceptibility, and digestive dysfunction in the neonate. These compositional defects may drive adverse "metabolic programming," predisposing offspring to immediate complications and long-term risks, including cognitive deficits and metabolic disorders. Consequently, strict management of maternal thyroid health is essential to preserve the biological quality of breast milk and optimize neonatal outcomes.