Amniotic fluid, “Premature” human milk, and “Term” human milk
Amniotic fluid contains amino acids, proteins, vitamins, minerals, hormones, and growth factors. While the concentration of these nutrients is much lower than that found in human milk, the large volumes of amniotic fluid swallowed in utero (up to a liter a day late in gestation, considerably more than the newborn consumes after birth) have a significant impact on growth and maturation of both the fetus and the fetal intestine.2 Animal studies and limited human observations suggest that swallowed amniotic fluid accounts for about 15% of fetal growth.3–5
Milk from women who deliver prematurely differs from that of women who deliver at term. Preterm milk is initially higher in protein, fat, free amino acids, and sodium, but over the first few weeks following delivery these levels decrease (Figure 1A). The mineral content (including trace minerals) of preterm milk is similar to that of term milk, with the following exceptions: calcium is significantly lower in preterm milk than term milk and does not appear to increase over time while copper and zinc content are both higher in preterm milk than term milk and decrease over the time of lactation.6, 7
Figure 1
Changes in milk composition over time in term (37–41 weeks), preterm (30–36 weeks) and very preterm (<28–30 weeks) infants. Data combined from multiple sources.15, 82, 115–122 GAG glycosaminoglycans, IL 6 interleukin ...
Lactose is the major carbohydrate in human milk. This disaccharide is an important energy source, is relatively low in colostrum, and increases over time with more dramatic increases in preterm milk (Figure 1A). Complex oligosaccharides are the second most abundant carbohydrate in human milk. These human milk oligosaccharides (HMOs) are not digestible by host glycosidases and yet are produced in large amounts with highly variable structures by the mother.8 HMOs appear to have three important functions: prebiotic (stimulation of commensal bacteria containing the bacterial glycosidases to deconstruct and consume the HMOs),9, 10 decoy (structural similarity to the glycans on enterocytes allows HMOs to competitively bind to pathogens),11 and provision of fucose and sialic acid that appear to be important in host defense and neurodevelopment respectively.12 Preterm milk is highly variable in HMO content. Differences between mothers are due to genetic diversity;13 there is also significant variability over time in content of fucosylated HMOs in individual mothers delivering preterm.14 Glycosaminoglycans (GAG) also appear to act as decoys providing binding sites for pathogenic bacteria to prevent adherence to the enterocyte. Premature milk is richer in GAG than term milk.15
Bioactive molecules in human milk are important components of the innate immune system. Differences in cytokines, growth factors and lactoferrin between preterm and term milk are most dramatic in colostrum and early milk and mostly resolve by 4 weeks after delivery (Figure 1B). Leptin is produced by mammary glands, secreted into human milk, and may be important in post-natal growth. Human milk leptin does not appear to differ between preterm and term milk.16 Bile salt-stimulated lipase activity is similar in term and preterm milk while lipoprotein lipase activity is higher in term milk.17
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