C 2016 July 01.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptWahlqvist et

C 2016 July 01.ML240 web Author Manuscript Author Manuscript Author Manuscript Author ManuscriptWahlqvist et al.Pyrvinium embonate solubility Pagebut the underlying mechanisms of programming remain unknown.75,76 While breastfeeding protects against later obesity in humans,77 animal data suggest distinct effects of maternal obesity on milk composition that program offspring for increased risk of obesity and metabolic disease.78,79 Krebs suggested that maternal phenotype (normal weight, NW versus overweight/obese, OW/Ob) may influence the nutrient profile (bioactive components) of human milk, thus influencing patterns of infant weight gain and fat deposition. Krebs’ group has compared the macronutrient content, cytokines, adipokines, and pro-oxidant mediators in human milk between two groups (NW and QW/Ob), and have related the findings to infant growth (n = 46) and body composition (n = 50) in the first 4 months of life in two separate studies.80,81 Their results identified hormonal differences in maternal circulation, but the general composition of human milk was similar between groups. Leptin and insulin were consistently higher in milk of OW/Ob women across time points (P < 0.05). However, macronutrients, adiponectin, ghrelin, and markers of oxidative stress in milk did not differ. The concentration of inflammatory cytokines in human milk also did not differ between the two groups, though the range and variability in cytokine concentrations may obscure meaningful differences.82 In a study assessing infant body composition, infants of OW/Ob mothers were heavier (P < 0.01) and fatter (P < 0.02) at birth. However, weight (adjusted for sex), percent body fat, weight gain, and fat deposition did not differ from NW comparisons thereafter. Another difference, the measured rate of infant lean mass gain was higher in infants of OW/Ob mothers. A multivariate model of infant lean mass deposition was constructed using backwards stepwise regression; in the final model, only three variables remained and explained 31 of the variability in lean mass deposition: infant sex and milk IL-10 concentrations were positively associated, while milk glucose concentrations were negatively associated, with the outcome. None of the biochemical compounds measured in milk was predictive of infant fat deposition over time.83 Similar results were detected in a second study of similar design that lacked measures of body composition: no differences in rates of infant weight gain were detected between groups. The most robust predictor of rate of infant weight gain over the first 4 months of life was caloric density of human milk at 4 months (P < 0.001).84 In addition to the biochemical composition of human milk, Krebs’ group assessed, in the larger cohort, maternal beliefs and behaviors surrounding infant feeding, as these have been hypothesized to play a role in development of later obesity.85 No differences in maternal beliefs between groups were detected, though OW/Ob women were more likely to feed their infants on a schedule by 4 months than were NW women (P < 0.03). Independent of maternal group, maternal concern about infant milk intake and/or weight gain was associated with a variety of poor outcomes, including less exclusive breastfeeding (P < 0.02), a “pressuring” feeding style (P < 0.01), and more feeding for infant fussiness (P < 0.01).Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAnn N Y Acad Sci. Author manuscript; available in PMC 2016 July 01.Wahlqvist et al.PageAccord.C 2016 July 01.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptWahlqvist et al.Pagebut the underlying mechanisms of programming remain unknown.75,76 While breastfeeding protects against later obesity in humans,77 animal data suggest distinct effects of maternal obesity on milk composition that program offspring for increased risk of obesity and metabolic disease.78,79 Krebs suggested that maternal phenotype (normal weight, NW versus overweight/obese, OW/Ob) may influence the nutrient profile (bioactive components) of human milk, thus influencing patterns of infant weight gain and fat deposition. Krebs’ group has compared the macronutrient content, cytokines, adipokines, and pro-oxidant mediators in human milk between two groups (NW and QW/Ob), and have related the findings to infant growth (n = 46) and body composition (n = 50) in the first 4 months of life in two separate studies.80,81 Their results identified hormonal differences in maternal circulation, but the general composition of human milk was similar between groups. Leptin and insulin were consistently higher in milk of OW/Ob women across time points (P < 0.05). However, macronutrients, adiponectin, ghrelin, and markers of oxidative stress in milk did not differ. The concentration of inflammatory cytokines in human milk also did not differ between the two groups, though the range and variability in cytokine concentrations may obscure meaningful differences.82 In a study assessing infant body composition, infants of OW/Ob mothers were heavier (P < 0.01) and fatter (P < 0.02) at birth. However, weight (adjusted for sex), percent body fat, weight gain, and fat deposition did not differ from NW comparisons thereafter. Another difference, the measured rate of infant lean mass gain was higher in infants of OW/Ob mothers. A multivariate model of infant lean mass deposition was constructed using backwards stepwise regression; in the final model, only three variables remained and explained 31 of the variability in lean mass deposition: infant sex and milk IL-10 concentrations were positively associated, while milk glucose concentrations were negatively associated, with the outcome. None of the biochemical compounds measured in milk was predictive of infant fat deposition over time.83 Similar results were detected in a second study of similar design that lacked measures of body composition: no differences in rates of infant weight gain were detected between groups. The most robust predictor of rate of infant weight gain over the first 4 months of life was caloric density of human milk at 4 months (P < 0.001).84 In addition to the biochemical composition of human milk, Krebs’ group assessed, in the larger cohort, maternal beliefs and behaviors surrounding infant feeding, as these have been hypothesized to play a role in development of later obesity.85 No differences in maternal beliefs between groups were detected, though OW/Ob women were more likely to feed their infants on a schedule by 4 months than were NW women (P < 0.03). Independent of maternal group, maternal concern about infant milk intake and/or weight gain was associated with a variety of poor outcomes, including less exclusive breastfeeding (P < 0.02), a “pressuring” feeding style (P < 0.01), and more feeding for infant fussiness (P < 0.01).Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAnn N Y Acad Sci. Author manuscript; available in PMC 2016 July 01.Wahlqvist et al.PageAccord.

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