Background: Overweight and obesity among children is an increasing concern, partly due to the substantial economic burden for the public health care system as childhood obesity increases the risk of obesity in adulthood with a subsequent risk of type 2 diabetes and cardiovascular diseases. With an increasing prevalence of the double burden of malnutrition, where under- and over nutrition coexist, overweight and obesity persist a major concern in a global perspective. The mechanisms whereby overweight and obesity are passed onto generations include foetal and lactational programming. Through inflammatory conditions as well as alterations of glucose and lipid metabolism during pregnancy, offspring of mothers with obesity may be predisposed to an altered appetite regulation as well as lipid and glucose metabolism. In early infancy, when physiological mechanisms may not be fully developed, orally ingested bioactives from human milk (HM) are posed to affect infant appetite regulation and possibly infant growth. Studies indicate that HM of mothers with compared to without obesity have elevated concentrations of the hormones leptin and insulin as well as cytokines including Tumour-necrosis factor-α and interleukin-6. As such, maternal health status may affect the infant during pregnancy and possibly lactation. However, the evidence for these mechanisms is strongest among women with obesity or with diseases such as gestational diabetes mellitus, and less is known about the mechanisms in mothers with normal- or overweight and without disease.

Objectives: The main objective was to explore the interplay between biomarkers of maternal inflammation during pregnancy and lactation and infant outcomes within a healthy population. Secondly, maternal predictors of inflammation during pregnancy and lactation were investigated.

Method: Data from Mothers, Infants and Lactation Quality (MILQ) was used in the present PhD thesis. The MILQ study is a cohort study including 1,000 healthy mother-infant dyads from Bangladesh, Brazil, Denmark and The Gambia with data collected at three time points from 1 to 8.5 months after birth. In Paper I, data from Denmark were used to investigate the mediating pathway by which appetite-regulating hormones (ARHs) arrive in HM. Data from a subgroup in Denmark were used in Paper II to explore associations between inflammatory-, lipid- and metabolic markers in pregnancy and pregnancy and breastfeeding outcomes. Data from all four cohorts were used in Paper III to compare HM concentrations of cytokines and ARHs between the sites as well as investigate the associations with infant growth.

Results: In Paper I, we found that leptin concentrations in HM were higher for mothers with body mass index (BMI) ≥25 kg/m2 compared to <25 kg/m2 with a higher mediated effect through plasma levels for mothers with BMI ≥25 kg/m2. A mediated effect was found in the association between maternal fat mass index and HM insulin, while no association was found neither for HM adiponectin nor between HM ARHs and infant outcomes. The findings support that leptin and insulin arrive in HM through maternal plasma, and to a higher degree for mothers with overweight.

In Paper II, higher levels of triglycerides and glucose following an oral glucose tolerance test were associated with higher birthweight adjusted for gestational age (GA), whereas higher levels of high-density lipoprotein were associated with a lower GA-adjusted birthweight and shorter duration of pregnancy and exclusive breastfeeding (EBF). Metabolic markers related to insulin resistance were positively associated with duration of EBF. Finally, higher pre-pregnancy BMI was associated with increased inflammatory and metabolic markers. The results indicate that lipid and glucose metabolism during pregnancy might affect foetal growth possibly through the placenta. Metabolic markers may affect duration of EBF, although these results were possibly confounded by mothers receiving breastfeeding counselling.

In Paper III, concentrations of cytokines and ARHs in HM differed significantly among the four sites of the MILQ study. Cytokines related to a T-helper cell type 2 (Th2) dominated immune response were highest in HM from Denmark, while concentrations of the three ARHs were highest in Brazil and lowest in Bangladesh. Furthermore, most cytokines in HM were inversely associated with weight-for-age and weight-for-length Z-scores in The Gambia. Our results indicate that cytokines in HM may reflect different environmental exposures, which possibly explain declining Z-scores identified in The Gambia.

The evidence of associations within HM research is sparse as the observational nature of most research studies often results in a substantial risk of confounding. However, results from the present PhD thesis indicate that maternal weight status may affect inflammatory biomarkers and metabolic alterations during pregnancy while also affecting HM composition of cytokines and ARHs. Furthermore, the alterations during pregnancy may affect foetal growth through the placenta. Finally, different environmental exposures are likely reflected in HM composition of cytokines, which possibly explain infant growth in certain populations. Breastfeeding remains an essential health promoting element in a global perspective, although more studies are needed to confirm the mechanisms and the influence on infant outcomes in healthy populations.