Overweight and obesity (OW/OB) impact half of the pregnancies in the United States and can have negative consequences for offspring health. Studies are limited on human milk alterations in the context of maternal obesity. Alterations in milk are hypothesized to impact offspring development during the critical period of lactation. We aimed to evaluate the relationships between mothers with OW/OB (body mass index [BMI] ≥25 kg/m²), infant growth, and selected milk nutrients. We recruited mother–infant dyads with pre‐pregnancy OW/OB and normal weight status. The primary study included 52 dyads with infant growth measures through 6 months. Thirty‐two dyads provided milk at 2 weeks, which was analysed for macronutrients, long‐chain fatty acids, and insulin. We used multivariable linear regression to examine the association of maternal weight status with infant growth, maternal weight status with milk components, and milk components with infant growth. Mothers with OW/OB had infants with higher weight‐for‐length (WFL) and BMIZ‐scores at birth. Mothers with OW/OB had higher milk insulin and dihomo‐gamma‐linolenic, adrenic, and palmitic acids and reduced conjugated linoleic and oleic acids. N6 long‐chain polyunsaturated fatty acid (LC‐PUFA)‐driven factor 1 was associated with higher WFL, lower length‐for‐age (LFA), and lower head circumference‐for‐ageZ‐scores change from 2 weeks to 2 months in human milk‐fed infants, whereas N6 LC‐PUFA‐driven factor 5 was associated with lower LFAZ‐score change. Human milk composition is associated with maternal pre‐pregnancy weight status and composition may be a contributing factor to early infant growth trajectory.

The window of lactation is a critical period during which nutritional and environmental exposures impact lifelong metabolic disease risk. Significant organ and tissue development, organ expansion and maturation of cellular functions occur during the lactation period, making this a vulnerable time during which transient insults can have lasting effects. This review will cover current literature on factors influencing lactational programming such as milk composition, maternal health status and environmental endocrine disruptors. The underlying mechanisms that have the potential to contribute to lactational programming of glucose homeostasis will also be addressed, as well as potential interventions to reduce offspring metabolic disease risk.

Overnutrition during critical windows of development plays a significant role in life-long metabolic disease risk. Early exposure to excessive nutrition may result in altered programming leading to increased susceptibility to obesity, inflammation, and metabolic complications. This study investigated the programming effects of high-fat diet (HFD) exposure during the lactation period on offspring adiposity and inflammation. Female C57Bl/6J dams were fed a normal diet or a 60% HFD during lactation. Offspring were weaned onto a normal diet until 12 weeks of age when half were re-challenged with HFD for 12 weeks. Metabolic testing was performed throughout adulthood. At 24 weeks, adipose depots were isolated and evaluated for macrophage profiling and inflammatory gene expression. Males exposed to HFD during lactation had insulin resistance and glucose intolerance as adults. After re-introduction to HFD, males had increased weight gain and worsened insulin resistance and hyperglycemia. There was increased infiltration of pro-inflammatory CD11c⁺ adipose tissue macrophages, and bone marrow was primed to produce granulocytes and macrophages. Bone density was lower due to enhanced marrow adiposity. This study demonstrates that maternal HFD exposure during the lactational window programs offspring adiposity, inflammation, and impaired glucose homeostasis.

In breastfed infants, human milk provides the primary source of iodine to meet demands during this vulnerable period of growth and development. Iodine is a key micronutrient that plays an essential role in hormone synthesis. Despite the importance of iodine, there is limited understanding of the maternal factors that influence milk iodine content and how milk iodine intake during infancy is related to postnatal growth. We examined breast milk samples from near 2 weeks and 2 months post-partum in a mother-infant dyad cohort of mothers with pre-pregnancy weight status defined by body mass index (BMI). Normal (NW, BMI < 25.0 kg/m²) is compared to overweight/obesity (OW/OB, BMI ≥ 25.0 kg/m²). The milk iodine concentration was determined by inductively coupled plasma mass spectrometry. We evaluated the associations between iodine content at 2 weeks and infant anthropometrics over the first year of life using multivariable linear mixed modeling. Iodine concentrations generally decreased from 2 weeks to 2 months. We observed no significant difference in iodine based on maternal weight. A higher iodine concentration at 2 weeks was associated with a larger increase in infant weight-for-age and weight-for-length Z-score change per month from 2 weeks to 1 year. This pilot study shows that early iodine intake may influence infant growth trajectory independent of maternal pre-pregnancy weight status.

Pancreatic β-cells are exquisitely sensitive to developmental nutrient stressors, and alterations in nutrient sensing pathways may underlie changes observed in these models. Here we developed a mouse model of in utero exposure to the anti-diabetic agent metformin. We have previously shown that this exposure increases offspring pancreatic β-cell mass at birth. We hypothesized that adult offspring would have improved metabolic parameters as a long-term outcome of metformin exposure. Virgin dams were given 5 mg/mL metformin in their water from E0.5 to delivery at E18.5. Body weight, glucose tolerance, insulin tolerance and glucose stimulated insulin secretion were analyzed in the offspring. When male offspring of dams given metformin during gestation were tested as adults they had improved glucose tolerance and enhanced insulin secretion in vivo as did their islets in vitro. Enhanced insulin secretion was accompanied by changes in intracellular free calcium responses to glucose and potassium chloride, possibly mediated by increased L channel expression. Female offspring exhibited improved glucose tolerance at advanced ages. In conclusion, in this model in utero metformin exposure leads to improved offspring metabolism in a gender-specific manner. These findings suggest that metformin applied during gestation may be an option for reprogramming metabolism in at risk groups.