25 Years of Research in Human Lactation: From Discovery to Translation

Abstract

Researchers have recently called for human lactation research to be conceptualized as a biological framework where maternal and infant factors impacting human milk, in terms of composition, volume and energy content are studied along with relationships to infant growth, development and health. This approach allows for the development of evidence-based interventions that are more likely to support breastfeeding and lactation in pursuit of global breastfeeding goals. Here we summarize the seminal findings of our research programme using a biological systems approach traversing breast anatomy, milk secretion, physiology of milk removal with respect to breastfeeding and expression, milk composition and infant intake, and infant gastric emptying, culminating in the exploration of relationships with infant growth, development of body composition, and health. This approach has allowed the translation of the findings with respect to education, and clinical practice. It also sets a foundation for improved study design for future investigations in human lactation.

Keywords: breast; breastfeeding; human milk; infant feeding; lactation; milk composition.

Figure 1

An overview of the structure of the review of our research programme from a biological systems perspective.

Figure 2

Sir Astley Cooper’s illustrations of the ductal system of the lactating breast. Duct were injected with coloured wax prior to dissection [6].

Figure 3

New understanding of the anatomy of the lactating breast. (a) Coopers ligaments (b) superficial and retromammary fat layers (c) milk duct system (d) macro anatomy of the breast. © Medela AG 2006. Used with permission.

Figure 4

Ultrasound images of milk ducts pre-milk ejection (a) and post-milk ejection (b). Milk ducts are imaged as black (anechoic). Post milk ejection the ducts are expanded with breast milk (Geddes et al., unpublished).

Figure 5

(a) Milk production of 792 mL with infant intake consisting of paired and single breastfeeds. (b) Milk production of 967 mL where the infant consumed 849 mL from the breast, 88 mL was expressed (Exp R + Exp L) and the infant consumed 108 mL of expressed breast milk (EBM).

Figure 6

Cyclic vacuum created by a breastfeeding infant. Baseline vacuum is the vacuum required to hold the nipple in place, elongate the nipple and seal to the breast. Peak vacuum is the strongest vacuum created by lowering the tongue during breastfeeding (Geddes et al, unpublished).

Figure 7

Ultrasound images of the infant oral cavity during breastfeeding (a) Tongue up position during breastfeeding. (b) Tongue down is drawn down to create a vacuum and milk flows into the oral cavity. ©Medela AG 2006. Used with permission.

Figure 8

Respiratory traces of a breastfeeding infant using respiratory inductive plethysmography. Signals are recorded from the ribcage (yellow) and abdomen (red) and the sum of the two is calculated (blue). Absence of signal reflects a swallow, downward slope an exhale and upward stope an inhale. Geddes et al., unpublished.

Figure 9

Possible pathways of lactocrine programming of the infant by the human milk proteins. BMI—body mass index; CDI—calculated daily intakes; Conc.—concentrations; doses—amounts of human milk component ingested during a single breastfeed; FFM—fat-free mass; FM—fat mass; %FM—percentage fat mass; GE—gastric emptying; MI—milk intake; PFSVs—post-feed stomach volumes; − negative association; + positive association. Purple arrows indicate the direct associations between components and infant BC. In the case where direct relationships between infant body composition and human milk components are supported by the relationships of human milk components with infant gastric emptying factors and breastfeeding parameters, these relationships have been included and could be integrated into possible pathway. Grey arrows indicate further possible pathways, although no direct association of component unit with infant body composition has been established (or not analysed in case of doses).

Figure 10

Possible pathways of lactocrine programming of the infant by the human milk immune factors. CDI—calculated daily intakes; FFM—fat-free mass; FM—fat mass; sIgA—secretory immunoglobulin A; − negative association; + positive association. Purple arrows indicate the direct associations between components and infant BC. In the case where direct relationships between infant body composition and human milk components are supported by the relationships of human milk components with infant breastfeeding parameters, these relationships have been included and could be integrated into possible pathway. Grey arrow indicates further possible pathway, although no direct association of component unit with infant body composition has been established.

Figure 11

Possible pathways of lactocrine programming of the infant by the human milk appetite hormones. BMI—body mass index; CDI—calculated daily intakes; Conc.—concentrations; doses—amounts of human milk component ingested during a single breastfeed; FFM—fat-free mass; FM—fat mass; %FM—percentage fat mass; GE—gastric emptying; MI—milk intake; − negative association; + positive association. Purple arrows indicate the direct associations between components and infant BC. In the case where direct relationships between infant body composition and human milk components are supported by the relationships of human milk components and infant gastric emptying factors and breastfeeding parameters, these relationships have been included and could be integrated into possible pathway. Grey arrows indicate further possible pathway, although no direct association of component unit with infant body composition has been established.

Figure 12

Possible pathways of lactocrine programming of the infant by the human milk glucocorticoids. BMI—body mass index; Conc.—concentrations; %FM—percentage fat mass; − negative association; + positive association. Purple arrows indicate the direct associations between components concentrations and infant BC and anthropometry.

Figure 13

Possible pathways of lactocrine programming of the infant by the human milk carbohydrates. BMI—body mass index; CDI—calculated daily intakes; Conc.—concentrations; doses—amounts of human milk component ingested during a single breastfeed; FFM—fat-free mass; FM—fat mass; GE—gastric emptying; HMO—human milk oligosaccharides; MI—milk intake; − negative association; + positive association. Purple arrows indicate the direct associations between components and infant BC. In the case where direct relationships between infant body composition and human milk components are supported by the relationships of human milk components with infant gastric emptying factors and breastfeeding parameters, these relationships have been included and could be integrated into possible pathway. Grey arrows indicate further possible pathways, although no direct association of component unit with infant body composition has been established (or not analysed in case of doses).

Figure 14

Beyond bacteria: relationships between human milk bacteria and other microbial and non-microbial components of milk. AMPs (antimicrobial proteins) have antibacterial effects, but are also liberated from their parent proteins via the proteolytic action of certain members of the milk microbiome [271]. Bacteriophages in milk can infect bacteria. Milk fungi have been both positively and negative correlated to milk bacteria [272]. HMOs are prebiotics which promote the growth of certain milk bacteria. SCFAs are both a product of a substrate for bacterial metabolism. Other bacterial metabolites such as indoles likely exist in milk. To characterise the influence of the human milk microbiome on infant health, an integrative analysis of these components is required.

Figure 15

Membrane enclosed structures isolated from human milk stained with neutral lipid stain Nile red (red) and DNA stain Draq5 (green). Scale bar represents 20 μm. Image provided by Ms. Isabel Schultz-Pernice.