Breastmilk and the Link to Overweight/Obesity and Maternal Diet in the Mother-breastmilk-child Triad

The global obesity pandemic continues to escalate, with projections showing 1 in 5 women and 1 in 7 men obese by 2030. Maternal obesity raises the risk of childhood obesity by 264%, and overweight/obese children are more prone to become obese adults.

Obesity-associated metabolic dysfunctions (inflammation, insulin resistance, dyslipidemia) heighten morbidity and mortality risks. Breastfeeding mitigates overweight/obesity risks, yet mothers with overweight/obesity often encounter challenges in initiation, continuation, and altered milk composition, showing elevated levels of leptin, insulin, and n-6/n-3 fatty acids. However, findings on other components, like total fat, fatty acids, insulin, adipokines, carotenoids, and immune factors, remain inconsistent due to methodological limitations and lack of comprehensive analysis. Nonetheless, the potential pro-inflammatory and obesogenic properties of milk produced by mothers with overweight/obesity have been discussed. Recent systematic reviews link breastmilk protein, fat, leptin, and IL-6 to infant growth and adiposity. Findings for other components remain unclear due to small samples, methodological limitations, and lack of a systemic approach to analyze breastmilk as a complex biological system. Alterations in breastmilk composition may stem from disrupted de novo synthesis, transport across the blood-breastmilk barrier, or altered circulating levels. Recent studies showed impaired de novo synthesis of C15:0 and C16:1 fatty acids, probably caused by insulin resistance and reduced long-chain fatty acid transfer linked to inflammation (suppress lipoprotein lipase activity essential for transporting lipid compounds). Hence, poor cardiometabolic status may mediate altered breastfeeding outcomes and milk composition, but it requires further studies. Studies among non-lactating individuals suggested lifestyle and diet play crucial roles in mitigating overweight/obesity metabolic implications (e.g., metabolically healthy obese (MHO) and metabolically obese with normal weight (MONW) phenotypes). Maternal diet can influence breastmilk concentration of certain diet-dependent nutrients and bioactives (e.g., fatty acids, vitamins A, D, and carotenoids). Similarly, prohealthy/unhealthy dietary patterns seem to have beneficial/unfavorable effects on breastmilk composition and breastfeeding outcomes, but results remain inconclusive. Nonetheless, some suggest that diet may mitigate the effects of maternal overweight/obesity on breastmilk composition in mothers with overweight/obesity. The mechanisms linking obesity-related changes in breastmilk to infant development remain unclear. This study addresses this gap by studying the mother-breastmilk-infant triad, focusing on maternal cardiometabolic status, diet, breastmilk composition as a complex biological system, and anthropometric and metabolic outcomes.

This study aims to elucidate the intricate interplay between maternal adiposity, cardiometabolic status, diet, and breastmilk composition and to understand the role of breastmilk in the transmission of obesity and the shaping of infant metabolic health.

Our research questions will aim to determine/explore the following questions:

Q1. How does the maternal BMI category differentiate breastmilk composition from a systemic perspective? Q2. How does maternal cardiometabolic status mediate OW/OB-related alterations in breastmilk composition? Q3. Whether (and how) maternal diet moderates OW/OB-related alterations in breastmilk composition? Q4. Whether (and how) maternal OW/OB differentiates infant metabolomic profile? Q5. Whether (and how) OW/OB-related alterations in breastmilk composition influence infant outcomes and obesity risk? Q6. Whether (and how) maternal dietary patterns moderate adverse health outcomes of maternal OW/OB in infants?

The research hypotheses assume that:

H1. Maternal OW and OB are associated with pro-inflammatory properties and altered breastmilk metabolome via obesity-related low-grade inflammation, metabolic alterations, and oxidative stress, not dietary differences.

H2. Metabolically healthy OW and OB mothers produce less altered breastmilk than metabolically unhealthy mothers, as cardiometabolic status mediates between adiposity and breastmilk composition.

H3. A pro-healthy dietary pattern attenuates, and a westernized dietary pattern exacerbates obesity-related alterations in breastmilk composition due to differences in concentrations of pro-, anti-inflammatory, and antioxidant dietary compounds.

H4. Infants of OW and OB mothers have altered growth trajectories and metabolic pathways, higher fat mass, and oxidative stress compared to infants of NW mothers.

H5. Obesity-related changes in breastmilk composition determine alterations in infant outcomes.

H6. Maternal pro-health/westernized dietary patterns and metabolic health mitigate/exacerbate the adverse effects of overweight and obesity on infant outcomes.

The investigators will verify these hypotheses based on results collected using gold standards and novel body composition assessment and analytical methods (DXA scans, HPLC, GC-MS, ELISA, and LC-MS), nutrient-based and dietary pattern-based dietary assessment with biomarkers validation, in-depth evaluation of maternal cardiometabolic status and infant outcomes, and a systemic approach to breastmilk composition analysis. The findings will lay the foundation for tailored, evidence-based interventions to disrupt the intergenerational transmission of obesity. Furthermore. contribute to advancing the health sciences discipline and decreasing the global health burden of overweight and obesity, supporting the realization of WHO's Global Nutrition Goals.

• Difference between groups and the change from 1 to 6 months postpartum in the maternal resting metabolic rate (RMR) [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and the change from 1 to 6 months postpartum in maternal dietary intake [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and the change from 1 to 6 months postpartum in maternal dietary habits [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and change from 1 to 6 months postpartum in maternal short- and long-term fatty acid status [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and change from 1 to 6 months postpartum in maternal and human milk lipophilic antioxidants and vitamins [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and the change from 1 to 6 months of life in infant skin carotenoid status [Срок оценки: 1, 3, 6 months of life]
• Difference between groups and change from 1 to 6 months postpartum in maternal and infant urine 8-isoprostane [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and change from 1 to 6 months postpartum in maternal serum hsCRP [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and change from 1 to 6 months postpartum in maternal serum IL-1 [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and change from 1 to 6 months postpartum in maternal serum IL-6 [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and change from 1 to 6 months postpartum in maternal serum TNF-alfa [Срок оценки: 1, 3, 6 months postpartum]
• Difference between groups and change from 1 to 3 months postpartum in human milk lipidomics [Срок оценки: 1, 3 months postpartum]