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AWHONN is accredited as a
provider of continuing nursing ABSTRACT
education by the American Nurses
Credentialing Centers In this article, we discuss the nutritional and immunobiological components of human milk that nurses need to know
Commission on Accreditation.
to offer optimal care and education to their patients and families. We describe the major macronutrients and micronu-
AWHONN holds a California BRN trients in human milk that are essential to the growth and development of the newborn infant, and we discuss the
number, California CNE Provider
#CEP580
immunobiological components of human milk that supplement and boost the newborns immune system.
JOGNN, 41, 122-137; 2012. DOI: 10.1111/j.1552-6909.2011.01314.x
http://JournalsCNE.awhonn.org
Accepted August 2011
Keywords
human milk
nutrition
immunobiological
anti-inflammatory
anti-infective
ewborn nutrition is of critical importance from (ABM, 2008), the Canadian Paediatric Society
Correspondence
Jae H. Kim, MD, PhD,
Pediatrics, UC San Diego
N a worldwide perspective. The choice be-
tween human milk (HM) and artificial nutrition is
(CPS) (Boland, 2005), the European Society for
Pediatric Gastroenterology, Hepatology and Nu-
Medical Center, 200 West one that every parent has to make, and a choice trition (NASPGHAN) (Agostoni et al., 2009), the
Arbor Dr., MPF 1140, San
Diego, CA 92103-8774
that will continue to be a challenging one for future World Health Organization (WHO) (2001), and the
neojae@ucsd.edu parents to make. Understanding the science be- United Nations Childrens Fund (UNICEF, 2003).
hind the benefits of HM and disseminating that
Jae H. Kim reports knowledge to parents of newborn infants is of In this article, we focus on what nurses need to
relationships with Abbot utmost importance to the medical and nursing know about the nutritional and immunobiological
Nutrition, Nutricia, and community. Human milk is an evolutionary wonder activity of HM to best prepare them for handling,
Medela as a presenter and
member of an advisory whereby the lactating mother produces a species- delivering, discussing, and promoting the use of
committee and has received specific nutritional and biologically active (bioac- HM for sick and healthy newborns.
an honorarium and research tive) product that confers the best health to the
grant.
human offspring. Human milk, like blood, is a liquid
tissue with cellular components, nutritional com-
Elizabeth B. Froh and
planners for this activity
ponents, and bioactive factors. Interestingly, the Nutritional Perspective
report no conflict of interest number of bioactive factors (>200) far outnum- Human milk is the ideal and preferred nutritional
or relevant financial bers the nutritional components in HM. source for all preterm and term infants throughout
relationships. The article the first year of life. Although the optimal duration
includes no discussion of
off-label drug or device use. These facts provide the basis for the recommen- of breastfeeding is unknown, most health orga-
No commercial support was dations that newborns have an exclusive diet of nizations currently recommend exclusive breast-
received for this HM from birth to age 6 months made by the feeding from birth to age 6 months. The AAP
educational activity.
following organizations: the American Academy further recommends a total duration of breastfeed-
of Pediatrics (AAP) Section on Breastfeeding ing for 1 year to maximize the full benefits of
(Gartner et al., 2005), the American College of Ob- breastfeeding (Gartner et al., 2005). The major
stetricians and Gynecologists (ACOG, 2005), the nutritional components of HM are macronutrients,
American Academy of Family Physicians (AAFP, micronutrients, vitamins, and trace elements (see
2007), the Academy of Breastfeeding Medicine Table 1).
http://jognn.awhonn.org
C 2011 AWHONN, the Association of Womens Health, Obstetric and Neonatal Nurses 122
Kim, J. H. and Froh, E. B. IN FOCUS
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Macronutrients
Fats. Fat is the largest single source of energy in With a sound knowledge base, the nurse can provide the
HM. The principal fat found in HM is in the form parents with the information needed to make an informed
of triglycerides (>98%) that are structurally three
decision regarding infant feeding.
fatty acids linked to a 3-carbon glycerol molecule.
The mammary gland packages these triglycerides
Human milk contains its own lipases, which is a
uniquely compared to the triglycerides found in
convenient design for improving fat digestion and
commercial infant formulas. The mammary ep-
is most active in fresh milk. The fat globules appear
ithelium processes triglycerides into membrane-
unaffected by refrigeration but may disrupt with
bound globules that contain a surface of gly-
freezing. The relevance of this disruption is with
coproteins, glycolipids, phospholipid, cholesterol,
some mothers, generally later in lactation, who
and enzymes with a dense triglyceride core (See
produce milk with high lipase activity. Their stored
Fig. 1). Fat globule size varies over the first week of
milk can develop a significant soapy or rancid
life postpartum and then gradually increases over
odor and taste, and infants may refuse to drink.
the next several months. This process appears to
Heat, such as that applied during pasteurization,
depend on the abundance of cell membrane from
can readily inactivate lipases. Unfortunately, no
which the globules are made (Michalski, Briard,
proven practical method for reducing lipase ac-
Michel, Tasson, & Poulain, 2005).
tivity without losing other bioactive properties is
available.
Unlike infant formula, the fatty acid profile in
HM highly reflects the dietary fatty acids of the
Fat digestion is superior in HM compared to that
mothers diet. For instance, a mother who eats
in formula milk. Triglycerides in HM are broken
a generous amount of omega-3 oil not typical of
down into free fatty acids and glycerol by the ac-
the North American diet will pass on these long
tivity of bile saltdependent and pancreatic lipase-
chain fatty acids into her milk and change the
related lipases found within HM (Lindquist &
fractional portion of omega-3 fats in her milk (Lau-
Hernell, 2010). The digestion of formula milk re-
ritzen & Carlson, 2011). A study in mother/infant
quires the primary activity of pancreatic lipases
dyads where mother and infant were supple-
that are more restrictive and digest triglycerides to
mented with omega-3 supplements during preg-
fatty acids and 2-mono-glycerol chains (one fatty
nancy and afterwards demonstrated an increased
acid in middle carbon position of a glycerol chain).
omega-3 content in mothers milk and favorable
As a result, some plant sources of triglycerides
outcomes in a subset of girls (Olsen et al., 2008).
found in formula milk have saturated fats in the
Fish oil taken by pregnant mothers may affect later
outer positions of the glycerol chain that make their
health outcomes in their children, as one longitu-
digestive products more prone to calcium bind-
dinal study found a reduced incidence of asthma
ing, soap formation, and subsequent energy loss
in infants of supplemented mothers (Smithers,
(Koo, Hockman, & Dow, 2006).
Gibson, McPhee, & Makrides, 2008). Trans fatty
acid content is a prime negative example of di-
Fat content in HM varies the most of any nutri-
etary influences on HM. Trans fatty acids was
ent component. This variation is largely due to the
prevalent in the North American diet, but after
graded increase in fat content of milk during a lac-
tighter regulation in the food industry resulted in
tation cycle where foremilk is relatively fat poor and
decreased levels of trans fatty acids in daily food,
hind milk is relatively enriched in fat and can con-
a corresponding reduction in trans fatty acids in
tain 3 times the fat content (Bishara, Dunn, Merko,
HM was seen (Friesen & Innis, 2006).
& Darling, 2008; Saarela, Kokkonen, & Koivisto,
2005). For the breastfed infant, this variability is Jae H. Kim, MD, PhD, is an
Fat digestion starts immediately with the activity
virtually unnoticeable due to the ingestion of all the associate professor of
of lipases secreted from the salivary glands and pediatrics in the Division of
milk. However, for the preterm or sick term infant
stomach. To digest these large globules of fat, Neonatal-Perinatal
where HM is pumped and stored, large variabil-
however, the membranes have to be broken down Medicine, University of
ity in fat content may be present. Using nonse- California San Diego, San
to allow access to the triglyceride core. Proper di-
quential delivery of milk may disadvantage an in- Diego, CA.
gestion of HM fat does require the presence of
fant to receive predominantly lower fat and thereby
bile acids, and therefore cholestatic infants may Elizabeth B. Froh, MS,
lower calorie milk. Nonsequential milk delivery is BSN, RN, is a pre-doctoral
not digest HM effectively. Once made accessible,
the delivery of stored milk without consideration of student in the School of
lipases found in the small bowel and secreted by Nursing, University of
matching the pumping sequence to the milk de-
the pancreas attack the free triglycerides. Pennsylvania, Philadelphia,
livery (Spatz, 2012).
PA.
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Table 1: Continued
Recognition of the physical properties of fresh HM rated out by ultracentrifugation or acid precipita-
is important. With large fat globules, the fat por- tion. The whey fraction of milk is digested better
tion of freshly expressed HM will readily sepa- than the casein fraction due to the faster transit
rate within minutes of expression with the lipids out of the stomach (Billeaud, Guillet, & Sandler,
rising to form a top layer. This separation of fat 1990). Bovine milk is casein dominant (> 80%),
is important to consider when storing and deliv- but most infant formulas have been altered now
ering milk to preterm infants. Warming and gen- to contain a greater whey fraction to mimic HM.
tle shaking of milk are important to perform prior Most of the bioactive factors in HM are in the
to feeding. Storage of milk in short-term refriger- whey fraction. The major whey protein produced
ated state or longer term frozen state does not ad- by the mammary gland is -lactalbumin. Other
versely affect fat content, but freezing may frac- whey proteins that resist digestion and are im-
ture membrane-bound globules (Vieira, Soares, portant for host defense include proteins such as
Pimenta, Abranches, & Moreira, 2011) (see lactoferrin, lysozyme, and secretory immunoglob-
Table 2). Substantial losses of adherent fat and ulin A (sIgA). The primary protein found in the ca-
nutrients can accumulate with multiple container sein fraction in HM, -casein, is highly phospho-
changes and long feeding tubes (Tacken et al., rylated enhancing its ability to bind calcium and
2009). Minimizing the number of transfers from confer improved calcium solubility (Bouhallab &
pumping to feeding is essential to prevent major Bougle, 2004). Free amino acids are present in
deterioration in milk quality. HM, the most abundant being glutamine, which
is not found in infant formulas because of prob-
Protein. The amino acid profile in HM proteins lems with stability of free glutamine. Glutamine is
is ideally balanced for the newborn. To achieve an important amino acid for cell growth, specifi-
this balance, numerous HM proteins are produced cally intestinal epithelial growth, has a role in im-
during lactation. Human milk proteins contain 70% mune function, and is a precursor in glutathione
whey and 30% casein fractions that can be sepa- synthesis.
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Nutrients
Vitamins B1, B2, B6, folic acid, C Vit C Vit C, folate, Vit B6
Protein digestion takes place through a series of peptides, urea, ammonia, free amino acids, cre-
digestive steps beginning in the stomach where atinine, creatine, nucleic acids, carnitine, amino
acid-activated pepsin starts cleaving protein. In sugars, low molecular weight peptide hormones,
the small bowel, the pancreatic juices are rich with and growth factors. Furthermore, total protein con-
endopeptidases and carboxypeptidases. These tent comprises both nutritional (digestible) and
peptidases digest long polypeptides by hydrol- nondigestible proteins, the latter being made up
ysis to tripeptides, dipeptides, and amino acids of the many bioactive proteins found in HM. Test-
that actively transport across the intestinal lumen ing macronutrient content is tricky with protein be-
(Boudry et al., 2010). Maternal dietary protein may cause the fractions of nonprotein nitrogen may
also be present in minute amounts and in sensitive contribute to the total nitrogen needs of the in-
infants lead to food protein sensitivity. This infant dividual whereas the nondigestible bioactive fac-
sensitivity commonly occurs with bovine protein tors do not add to the total nitrogen intake. Ref-
intake in mothers (Solinas, Corpino, Maccioni, & erence chemical analysis does not account for
Pelosi, 2010; Wilson, Self, & Hamburger, 1990). the digestibility of these proteins but can separate
Many of the protein components, however, are bi- out true protein from nonprotein nitrogen. Infant
ologically active, resistant to digestion, and func- formulas, therefore, may have inadvertently over-
tion in a myriad of ways to improve gut function estimated the amount of nutritional protein that is
through alterations in the gut immune, digestive, required (Hosoi et al., 2005).
and nervous system.
Like fat, protein content in HM can vary consider-
Proteins are not the only source for nitrogen in ably over the lactation period. Most importantly is
HM. The total nitrogen content in HM represents a steady decline in protein content over the first
the sum of protein nitrogen and nonprotein nitro- month of life (20%25%) with more gradual de-
gen. Numerous nonprotein nitrogen sources are clines (4%/month) over the subsequent months
found in HM and include compounds such as (Saarela et al., 2005). This protein content change
is particularly relevant when using donor HM that provide optimal mineral metabolism for the grow-
is generally obtained from lactating donors sev- ing infant. Calcium (Ca) and phosphorus (P) ex-
eral months into their lactation period. Variabil- ist in ionized and complex forms that are easily
ity in protein content seen between mothers is absorbed. Preterm HM contains only minimally
poorly understood and is not well correlated with higher amounts of Ca and P compared to term
daily diet. A study where mothers ingested ei- HM (Bauer & Gerss, 2011). Due to the rapidity
ther very high- or low-protein diets found that of growth of the preterm infant compared to the
a high-protein diet increased nitrogen levels but term infant, additional mineral supplementation is
mostly due to increased urea (Forsum & Lon- required. The ratio of Ca and P increases over the
nerdal, 1980). For not fully understood reasons, lactation period with gradually lower phosphorus
preterm milk contains more protein that term milk, levels. Magnesium (Mg) is another essential com-
which is an advantage because preterm infants ponent of bone mass given that bone contains
require more protein to grow adequately. approximately 60% of the bodys Mg. The absorp-
tion of Mg is significantly greater in unfortified HM
compared with formula and therefore additional
Carbohydrates. The carbohydrate fraction of HM
Mg is not required in HM feeding (Dorea, 2000).
comprises two major components, 90% to 95%
lactose and 5% to 10% HM oligosaccharides
(HMO). The lactose content of HM rises from Iron. Iron is an essential nutrient for normal cogni-
55 g/L in colostrum to 70 g/L in mature milk. Lac- tive development. The iron in HM is found bound to
tose content correlates positively with milk volume several different components including lipids, the
and negatively with whey protein content due to aqueous portion (20%30% with lactoferrin), and
its high osmotic properties. Besides providing an casein (10%). The bioavailability of iron is fivefold
abundant carbon source for energy, dietary lac- higher for HM as compared to infant formula milk.
tose also has been associated with increased min- The concentration of iron in HM declines through
eral absorption (Klein, 2002). Digestion of lactose lactation, from approximately 0.6 mg/L at 2 weeks
into glucose and galactose occurs in the pres- to 0.3 mg/L after 5 months of lactation (Siimes,
ence of intestinal lactase found on the brush bor- Vuori, & Kuitunen, 1979). Although the iron needs
der membrane of the intestinal mucosa. Galac- are met with HM in the exclusively breastfed term
tose is essential for the production of galacto-lipid infant, preterm infants require additional supple-
products like cerebrosides that are important in mentation to maintain their iron stores (Agostoni
central nervous system development. The pres- et al., 2010; Kleinman, 2009).
ence of a small amount of lactose in the stool of
term infants is assumed a normal physiological
Vitamins. Good bone health requires adequate
effect of feeding HM. A softer stool consistency,
mineral supply and vitamin D. The low content
more nonpathogenic bacterial fecal flora, and im-
of vitamin D in HM raises major health concerns
proved absorption of minerals attribute to the pres-
for the exclusively breastfed infant. Therefore,
ence of small quantities of unabsorbed lactose
the AAP recommends vitamin D supplementa-
in feces (Klein). The feeding of HM in premature
tion for the exclusively breastfed infant. Interest-
infants stimulates intestinal lactase activity com-
ingly, the amount of vitamin D directly correlates
pared with no feeding or formula feeding and thus
with maternal vitamin D stores. This correlation
permits early tolerance to lactose containing milk
raises the interesting hypothesis that greater ex-
(Shulman et al., 1998). Because of earlier con-
posure to sunlight in human history led to much
cerns regarding lactose utilization by premature
higher amounts of vitamin D in maternal milk and
infants resulting in attempts to reduce the osmo-
may not be a fixed deficiency of HM. Indeed,
lality of the milk, preterm formulas contain a large
high maternal supplementation has demonstrated
proportion of carbohydrate as corn syrup solids or
to improve milk vitamin D levels (Basile, Taylor,
glucose polymers (Klein). Human milk oligosac-
Wagner, Horst, & Hollis, 2006). Fresh HM con-
charides are resistant to digestion and likely have
tains ample amounts of water-soluble vitamins,
mostly nonnutritional roles in the gut as discussed
thiamin, riboflavin, niacin, vitamin B6, folate, vi-
in detail below.
tamin B12, pantothenic acid, biotin, and vitamin
C. These vitamins are not stored in the body, and
Micronutrients excess intakes are excreted in the urine or bile
Calcium, Phosphorus, Magnesium. Bone health (vitamin B12). However, some B vitamins and vi-
of the newborn is dependent on an abundant sup- tamin C are more prone to degradation or ox-
ply of minerals. Human milk is well designed to idation with exposure to heat, light, or air (Van
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Zoeren-Grobben, Schrijver, Van den Berg, & energy in HM may be erroneous due to the differ-
Berger, 1987). ences between bovine and HM. Calculated values
for energy may overestimate the caloric density of
HM by more than 10% (Hosoi et al., 2005). The im-
Trace Elements. Trace elements such as zinc
plications of this may be that formula may contain
(Zn), copper (Cu), selenium (Se), manganese
excessive energy.
(Mn), chromium (Cr), and cobalt (Co) are found
in adequate amounts in HM for the healthy term
Mothers who continue lactation through to their
infant. Zinc actively engages with different en-
next pregnancy (called tandem nursing) may alter
zymes in catalytic, structural, and regulatory roles
their milk volumes and composition as a direct
that are essential for growth. Low maternal Zn sta-
result of the physiologic changes during preg-
tus can reduce Zn content of HM (de Figueiredo,
nancy. The limited studies available suggest that
Palhares, Melnikov, da Cruz Montes Moura, & Dos
lactation has a variable response to a concur-
Santos, 2009). Copper has a catalytic role in re-
rent pregnancy (Marquis, Penny, Diaz, & Marin,
ducing molecular oxygen through its binding to
2002; Marquis, Penny, Zimmer, Diaz, & Marin,
superoxide dismutase, a critical enzyme in antiox-
2003; Merchant, Martorell, & Haas, 1990). One
idant defense. Copper levels gradually reduce in
may see a reduction or no effect on total milk vol-
amount over the lactation period (Abdulrazzaq,
ume, and infants may experience either a small
Osman, Nagelkerke, Kosanovic, & Adem, 2008).
reduction or no effect in weight gain compared
Selenium is a key component in glutathione syn-
to breastfed infants not fed by pregnant mothers.
thetase and does not need to be supplemented
Small changes in bioactive factors have also been
(Valent, Horvat, Mazej, Stibilj, & Barbone, 2011).
noted. Throughout the world, tandem nursing is
Manganese is essential for growth, development,
practiced safely, but further studies are required
and maintenance of health, but recommendations
to elaborate on the optimal feeding strategy with
for Mn intake are poorly defined. Deficiencies in
multiple infants.
Mn have not been described with exclusive HM
intake, and therefore the trace amounts of Mn in
HM are adequate for health. Chromium needs are
The Immunobiological Perspective. The immuno-
closely associated with insulin activity at the re-
biological advantages associated with an exclu-
ceptor level, and sufficient amounts of Cr can be
sive HM diet are critical for the healthy and the
found in HM.
preterm or vulnerable newborn. A diet of exclu-
sive HM will supply the infant with a multitude
Content and Calorie Variability. Numerous factors of protective elements to establish critical host
lead to changes in macronutrient content, and defense systems (Piper, Berry, & Cregan, 2007;
many of these factors are not well understood. Rodriguez, Miracle, & Meier, 2005; Wold & Adler-
Variability in nutritional content of HM is well known berth, 2000). Human milk consists of specific el-
and thought to be a result of differences between ements designed to enhance the newborns im-
pumping fraction (hindmilk vs. foremilk), time of mune system. The components of HM, such as
day, day of lactation, and degree of breast empty- secretory IgA, lactoferrin, and lysozyme, are mul-
ing (Hale & Hartmann, 2007). Low-calorie foremilk tifunctional and serve to protect the infant through
may contain as few as 12 kilocalories/ounce, and various interactions. Some of these advantages in-
high-calorie hind milk may contain as many as clude an added immune defense by means of im-
30 kilocalories/ounce (Hosoi et al., 2005; Sauer & munoglobulins, oligosaccharides, cytokines, and
Kim, 2011). The most variable component in HM is glycoproteinsprotecting the newborn from in-
fat, and because fat has the highest caloric den- fective agents (Hosea Blewett, Cicalo, Holland,
sity, great fluctuations in total energy has been & Field, 2008). Immune cells, long-chain polyun-
observed. Single daily pooling of pumped milk saturated fatty acids, cytokines, nucleotides, hor-
eliminates the inherent variability in multiple daily mones, and bioactive peptides also play a vital
sampling. Individual samples can vary tremen- role in aiding the immune system of the newborn
dously for fat, protein, and carbohydrates. (Hosea Blewett et al.; Lawrence & Pane, 2007;
Newberg & Walker, 2007; Riordan & Wambach,
Part of the problem with energy expenditure mea- 2010). Distinct advantages of the ingestion of HM
surements with calorimetry is that components of in the newborn period include improved gut bar-
HM that are resistant to digestion will be com- rier protection, bacterial cell wall lysis, preven-
busted alongside those that are absorbed. Use tion of inflammation, and the creation of an ideal
of standard conversion tables to calculate total gut microflora (Niers, Stasse-Wolthuis, Rombouts,
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6% to 10% of lactoferrin reaches the infant colon veloping immune system, HM offers the neces-
undigested and could function as a prebiotic (Le sary passive immunity (via maternal immunoglob-
Huerou-Luron et al., 2010; Riordan & Wambach, ulins in HM) and prolonged immunological
2010). From a rat model of necrotizing enterocol- support needed in the newborn period of life
itis, Sherman Sherman, Bennett, Hwang, and Yu (Niers et al., 2007).
(2004) introduced combinations of lactoferrin and
Lactobacillus GG (a probiotic) into rat pups that Secretory Immunoglobulin A. Immunoglobulins or
typically do not ingest lactoferrin in their milk. They antibodies are key anti-infective components of
showed the combined effect of lactoferrin and a HM. Immunoglobulins are proteins that are pro-
probiotic enhanced the rats defenses against in- duced by plasma cells in response to a foreign
fective enteric pathogens such as Escherichia coli disease cell or particle. They identify and have the
in the small intestines. The primary mechanism ability to neutralize or act on particular antigens.
may be through the iron-binding capacity of lacto- Although five immunoglobulins are present in HM,
ferrin in removing accessible iron from the gut lu- the most important one is secretory immunoglobu-
men preventing some pathogenic bacteria from lin A (IgA). Immunoglobulin A is responsible for the
growing. Lactoferrin may act as a potent adjunct to prevention of bacteria and viruses from binding
oligosaccharides in preventing bacterial disease to mucosal surfaces, neutralizing microbial tox-
in infants (Sherman et al.). ins, and increasing virus excretion in the newborn
(Hosea Blewett et al., 2008; Le Huerou-Luron et al.,
Acknowledgment of the effects of temperature 2010). Secretory IgA (sIgA) antibodies are synthe-
such as during pasteurization on levels of lactofer- sized and stored in the maternal breast. Found in
rin in HM is important. Concentrations of lactoferrin highest concentration in the maternal colostrum
were 44% lower in pasteurized HM (P = .002) than (10 g/L), sIgA is the major immune defense in the
in fresh HM (Akinbi et al., 2010; Hosea Blewett newborns intestines and offers protection against
et al., 2008). However, no significant difference gastrointestinal infections (Chirico, Marzollo, Corti-
in the concentrations of lactoferrin between fresh novis, Fonte, & Gasparoni, 2008; Thapa, 2005). In-
and frozen HM was found (Akinbi et al.). terestingly, mothers of critical or sick infants have
higher levels of sIgA in their breast milk (Feist,
Berger, & Speer, 2000). Along with lactoferrin, sIgA
Anti-Infective Properties of HM. Numerous anti- resists digestion and finds its way into the intestinal
infective components of HM offer the infant robust tract of the newborn (Niers et al., 2007). Together
protection against infection (see Table 1). Human these two elements make up approximately 30%
milk consists of specific elements designed to of proteins found in HM (Hosea Blewett et al.).
enhance the newborns immune system. Human
milk bioactive factors such as immune cells, long- Although levels of sIgA remain stable in mature
chain polyunsaturated fatty acids, cytokines, nu- HM, providing the infant with as much fresh HM as
cleotides, hormones, and bioactive peptides play possible to obtain maximum benefits is important.
a vital role in aiding the immune system of the The mean concentration of sIgA in HM is reduced
newborn (Hosea Blewett et al., 2008). The anti- by approximately 51% when the HM is frozen, by
infective components of HM are effective against 60% when the milk is pasteurized (P < 0.0001),
pathogenic bacteria including Escherichia coli, and by 98% when microwaved (Akinbi et al., 2010;
Vibrio cholerae, Campylobacter, Shigella, Giardia Lawrence, 1999; Tully, 2000).
lambia, and Pneumococcus as well as in the viral
defense against rotavirus, cytomegalovirus, in-
Lactoferrin. Lactoferrin is an essential compo-
fluenza virus, and respiratory syncytial virus (Han-
nent of the immune response (Coppa et al.,
cock et al., 2002; Hosea Blewett et al., 2008; Wold
2006; Le Huerou-Luron et al., 2010). Lactoferrin
& Adlerberth, 2000). Even partial daily feedings of
has strong antimicrobial activity against multiple
HM reduces the risk of nosocomial infections in
pathogens including bacteria, fungi, viruses, and
premature infants by 50% (Furman, Taylor, Minich,
protozoa. Lactoferrin can directly disrupt microbial
& Hack, 2003; Rodriguez et al., 2005). Therefore,
cell membranes and is an essential growth factor
HM confers to the newborn increased protection
for B- and T-lymphocytes (Riordan & Wambach,
from such infections as gastroenteritis, upper and
2010). Lactoferrin also promotes epithelial growth
lower respiratory tract infections, urinary tract in-
(Labbok, Clark, & Goldman, 2004). Lactoferrin has
fections, neonatal septicemia, necrotizing entero-
strong affinity for iron and is thought to constrict the
colitis, and acute otitis media (Wold & Adlerberth,
available free iron in the gut away from pathogens.
2000). Working in tandem with the newborns de-
Lysozyme. Lysozyme is a major protein found tionales for using fresh HM when possible to ob-
in HM with anti-infective and anti-inflammatory tain the benefits of its native phagocytes such as
properties. Lysozyme in tandem with lactofer- macrophages and neutrophils.
rin has proven bactericidal effects (Lonnerdal,
2003; Newberg, 2005; Newberg, Ruiz-Palacios, & The majority of leukocytes in HM are neu-
Morrow, 2005). Through cell wall lysis, lysozyme trophils (40%65% of total leukocytes), mono-
destroys such pathogenic bacteria including cytes/macrophages (35%55%), and either B- or
Escherichia coli and Salmonella (Riordan & T-lymphocytes (Niers et al., 2007). B-lymphocytes
Wambach, 2010). Concentrations of lysozyme produce antibodies whereas T-lymphocytes are
are higher in HM than bovine milk and progres- part of the cell-mediated immune response (Niers
sively increase with the duration of breastfeeding et al.). An integral component of the secretory im-
and/or pumping (Hettinga et al., 2011; Riordan & mune system, lymphocytes circulate through mu-
Wambach, 2010). cosal lymphoid tissues becoming sensitized to
antigens found in the respiratory and gastrointesti-
nal tracts (Chirico et al., 2008). Most HM lympho-
Oligosaccharides. One of the primary ways
cytes act locally within the gut to augment the in-
oligosaccharides function is by counteracting the
testinal immune system.
ability of pathogens to bind to the newborns host
cell receptors (Niers et al., 2007). They are also re-
sistant to digestion and can therefore easily bind Pancreatic Secretory Trypsin Inhibitor. A recently
to host cell receptors in the newborns gut (New- identified component of HM called pancreatic se-
berg et al., 2005). This action ensures protection cretory trypsin inhibitor (PSTI), a 56-amino acid
against some of the bacterial and viral pathogens peptide, was found to be responsible for the pro-
found in the gastrointestinal system. For example, tection of the pancreas from autodigestion, along
oligosaccharides have the ability to bind to the with having additional health benefits to the ani-
intestinal mucosa and protect the breastfed new- mal and human gut (Marchbank, Weaver, Nilsen-
born from enteric pathogens that may lead to di- Hamilton, & Playford, 2009). Found in highest
arrhea (Morrow et al., 2004). concentrations in maternal colostrum, PSTI is typ-
ically expressed in the mucus-producing cells of
Human milk has a great diversity of glycan expres- the stomach and large intestine and secreted into
sion and differs in specific types of glycans due gastric juice where it protects the mucus layer form
to environmental as well maternal genetic factors excessive digestion (p. 697). This peptide stim-
and stage of lactation (Newberg, 2008). This diver- ulates intestinal cell line migration; and through
sity further distinguishes HM from other artificial a process of restitution, the surviving cells are
feeding alternatives. able to migrate over the wounded area. Using
an animal rat model, the authors compared rats
fed via gavage human breast milk to rats receiv-
White Blood Cells. Human milk contains numer-
ing a commercial formula feed. Gastric damage in
ous different cellular components that contribute
their model was reduced by 75% among rats fed
to anti-infective defense. Approximately 90% of
HM over the rats fed commercial formula. When
the white blood cells found in HM are phagocytes
applied to a human population, the authors rec-
including macrophages and neutrophils (Riordan
ommend that feeding neonates human colostrum
& Wambach, 2010). Macrophages are large cells
will aid in the establishment and maintenance of
that ingest pathogens and other cell debris. Upon
human gut integrity (Marchbank et al.).
phagocytosis, the macrophage displays an anti-
gen, produced by the foreign substance, on its
cell surface for other cells to recognize. Addi- Xanthine Oxidase. Hancock et al. (2002) iden-
tionally, macrophages, known to release the im- tified the connection between xanthine oxidase
munoglobulin IgA, are the chief antibody in the (XO), an essential enzyme found in HM, and spec-
membranes of the respiratory and gastrointesti- ified antimicrobial properties. The authors studied
nal tracts responsible for mucosal immunity (Rior- the effects of bovine and HM on the metabolic
dan & Wambach). However, the number of cells activity of Escherichia coli. Located on the outer
present in HM is reduced dramatically by storing, surfaces of fat globules, XO attracts pathogens
freezing, pasteurization, microwaving, and soni- to bind to it therefore diverting bacteria away
fication (Lawrence, 2001). Therefore, this reduc- from their target (inclusive of the digestive tract).
tion in the number of macrophage cells resulting Found in highest concentrations in the maternal
from HM processing is one of the strongest ra- colostrum, XO is a valuable protective component
CNE
http://JournalsCNE.awhonn.org
Figure 1. Structure of human milk fat globule. From Michalski, M. C., Briard, V., Michel, F., Tasson, F., & Poulain, P. (2005). Size
distribution of fat globules in human colostrum, breast milk, and infant formula. Journal of Dairy Science, 88(6), 19271940.
Printed with permission from Elsevier.
CNE
http://JournalsCNE.awhonn.org
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stay is important. weight infants born at less than 28 weeks gestation. Journal of
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