Determinants of human milk composition: impact of methodology, maternal obesity and dietary intake

Abstract

Human milk (HM) is uniquely designed for the infant, containing the nutrients and bioactive components that are required to support growth and development, and is known for its important role in infant health. However, it is becoming increasingly clear that the composition of HM varies considerably between mothers, and that these differences may affect the short and longer-term health of the child. The composition of HM varies across lactation and even within a single feed, and as a result the method of HM sample collection can have a significant impact on the results of compositional analyses and complicate comparisons between studies. Therefore, the first part of this thesis details the design and outcomes of a systematic review describing the different collection methodologies applied in studies assessing HM composition and comparing the results obtained for HM macronutrient composition. The results of this systematic review were used to inform development of recommendations for a robust, consistent and practical sampling approach as an alternative to pooled 24-h collections – which has been referred to as the ‘gold standard method’, but which carries a relatively high participant burden and is impractical for large population studies. In addition to the method of collection (pre-feed, post-feed or pooled samples collection), it was also unclear to what extent HM macronutrient concentrations changed over periods of days to weeks and according to collection breast, and thus what frequency of sampling would be required to obtain representative results for HM composition of an individual. The next chapter aimed to complement the previous study by systematically evaluating the impact of day of collection during the week, time of day of collection and collection breast on HM macronutrient concentrations. The results of this study suggested that the pragmatic approach of collecting pre-feed samples at the same time point during the day, and at one time point over a 3-week period, provided a reliable estimate of mature HM composition for an individual, irrespective of the breast of collection. Previous studies had provided evidence that maternal overweight and obesity were potentially associated with alterations in HM composition, and that these may have a role in the intergenerational cycle of obesity. However, the extent of these differences across the full complement of nutritional factors and metabolic hormones in HM was unclear. The second part of this thesis reports the results of a systematic review and meta-analysis describing the effects of maternal obesity on the levels of macronutrients and metabolic hormones in HM. These studies suggest that maternal overweight and obesity are associated with altered concentrations of fat, lactose and key metabolic hormones in HM. While these findings suggest that maternal obesity can impact HM composition, the mechanisms underlying these changes, in particular whether they were driven by metabolic or dietary factors was unclear. Further, the impact of changes to specific components of the maternal diet while breastfeeding on HM composition was unclear. To address this knowledge gap, we undertook a proof of concept clinical trial to assess the effect of improving dietary quality during breastfeeding on the concentrations of macronutrients and metabolic hormones in HM. The study indicated that significant reductions in maternal energy, carbohydrate, fat and sugar intake over a 2-week period were effective in reducing maternal weight and body fat mass and were associated with reduced concentrations of leptin, insulin and adiponectin in HM, but did not affect HM macronutrient composition, milk production or infant growth. In conclusion, this thesis has made a significant contribution to the field of HM research. The research has provided evidence-based recommendations as to a HM sampling protocol for improving replicability and consistency between studies, a contemporary synthesis of information on the impact of maternal obesity on HM composition and novel direct evidence of the impact of improved maternal diet quality on HM composition and production. These data are critical given the established importance of nutritional exposures in early infancy for an individual’s life-long health outcomes, and therefore the potential impact of altered HM composition on long-term health of the child.