Breastfeeding: More Than Just Good Nutrition

Abstract

After completing this article, readers should be able to: Over the past 50 to 60 years, human milk has been described and recognized as the best first food for human infants; breast is best! Human milk provides substantial nutritional, cognitive, emotional, and immunologic benefits for the infant. Such ongoing acclamation is based on the observations and experiences of mothers, families, midwives, doulas, nutritionists, nurses, physicians, and scientists.Over the past 30 years, scientific study and research have accumulated and now constitute a large body of evidence documenting the actual benefits of breastfeeding for the infant and the mother. This article examines and references much of this evidence-based data in describing human milk and how it contributes to the health and well-being of infants and mothers.The Agency for Healthcare Research and Quality (AHRQ) Report on Breastfeeding in Developed Countries summarizes evidence (published in English through May 2006) on breastfeeding in maternal and infant health. (1) More than 9,000 abstracts were considered, and data from more than 400 individual studies were included after evidence-based review of meta-analyses, updated systematic review of the data, and newly performed systematic reviews. It is important to emphasize that this report included data from developed countries only. Table 1presents definitions of breastfeeding that are particularly useful in “quantification” as standard definitions used in clinical studies.Nineteen specific outcomes were reviewed by the AHRQ research team, including 13 for term infants and six for mothers. The outcomes for infants were: incidence of acute otitis media, atopic dermatitis, gastrointestinal (GI) infections, lower respiratory tract infections, asthma, obesity, type 1 and 2 diabetes, childhood leukemia, infant mortality, and sudden infant death syndrome as well as cognitive development and the risk of cardiovascular disease. Factors studied in mothers were: return to prepregnancy weight and incidence of type 2 diabetes, osteoporosis, postpartum depression, breast cancer, and ovarian cancer.For infants, the meta-analyses or systematic reviews strongly favored breastfeeding over not breastfeeding for a reduced risk of acute otitis media, GI infections, asthma (regardless of whether there was a family history of asthma), type 2 diabetes, leukemia, and sudden infant death syndrome. The meta-analysis of GI infections reported a crude odds ratio for 14 cohort studies of 0.36 (95% confidence interval [CI] 0.32 to 0.41) strongly favoring breastfeeding (ever) in reducing the risk of GI infection in infants younger than 1 year of age (Fig. 1). Another analysis reported on two case-control studies demonstrating a summary odds ratio of 0.54 (95% CI 0.36 to 0.80) again favoring breastfeeding. A separate analysis demonstrated that infants breastfeeding exclusively for greater than 3 months' or greater than 6 months' duration had significant reductions in the risk of acute otitis media compared with infants who were never breastfed. The analysis of infants developing atopic dermatitis (who had a family history of atopic disease) demonstrated that the risk for atopic dermatitis was lower in infants breastfed exclusively for longer than 3 months compared with children who were breastfed for less than 3 months. An analysis examining lower respiratory tract infections showed an overall reduced risk of hospitalization due to lower respiratory tract infections in infants (<1 year of age) who were breastfed exclusively for 4 months or longer compared with infants who were never breastfed (Fig. 1).The report presented two meta-analyses and a systematic review demonstrating a reduced risk of breast cancer associated with breastfeeding primarily in premenopausal women. One meta-analysis that included 45 studies showed a 4.3% reduction in risk for each year of breastfeeding. A second meta-analysis that included 23 studies demonstrated a 28% reduced risk of breast cancer for 12 months or more of breastfeeding. The AHRQ team performed a meta-analysis of 9 “fair” quality studies that included 4,387 cases of ovarian cancer and more than 10,000 controls. This new meta-analysis showed an association between breastfeeding and a reduced risk of ovarian cancer. Cumulative lifetime breastfeeding duration of more than 12 months was associated significantly with a decreased risk of ovarian cancer compared with never breastfeeding. This benefit was not seen for cumulative duration of breastfeeding of less than 12 months (Fig. 2). Additional data are needed to confirm a dose-response relationship between breastfeeding and a reduced risk of ovarian cancer.The analysis for type 2 diabetes, involving two very large cohort studies, showed that breastfeeding was associated with a reduced risk of developing type 2 diabetes in women who did not have a history of gestational diabetes. Each additional year of lifelong breastfeeding was associated with a 4% to 12% risk reduction in the two different cohorts. Breastfeeding did not appear to lead to a reduced risk of developing type 2 diabetes in women who had gestational diabetes. The studies on return to prepregnancy weight, osteoporosis, and postpartum depression were unable to demonstrate an association between breastfeeding and these specific maternal health outcomes due to methodologic issues and the effect of other contributing factors or confounders.These high-quality, evidence-based data from the AHRQ Report support breastfeeding as providing significant health benefits to both the mother and infant, even in developed countries. A larger body of evidence from developing countries examines the benefits of breastfeeding in locales where the risk of infection in infants and children is high due to poor sanitation, low water quality, contaminated food sources, and other variables. This benefit is well documented for diarrheal disease, respiratory infections, and otitis media.Beyond the evidence-based medicine measures is the realm of attachment and bonding between infant and mother and the psychological and developmental benefits of breastfeeding for the mother and infant. How these spheres are influenced by breastfeeding has been studied extensively in many different countries and cultures. Close and frequent contact between the mother and infant, especially skin-to-skin contact, affects the mother's attachment to the infant positively. The positive feelings affected by the close (skin-to-skin) and frequent early contact facilitate successful breastfeeding, longer duration of breastfeeding, and more attachment behavior (fondling, kissing, and caressing the infant). Recognition of these effects has led to more direct contact between the infant and his or her parents in the delivery and postpartum areas. Such recognition has supported the recommendation to allow placement of the infant in direct skin-to-skin contact with the mother in the first hour after birth to encourage successful breastfeeding. The multiple contributory factors to infant development makes it difficult to demonstrate a causative connection between early skin-to-skin contact or breastfeeding and overall infant and child development, emotional stability, personality, attachment, or person-to-person interactions.The impact of different methods of feeding infants on the onset of allergy has been researched. A meta-analysis of 18 prospective studies involving term infants who had a family history of atopy found a reduction of 42% (95% CI, 8% to 59%) in the risk of atopic dermatitis for infants breastfed for at least 3 months compared with those who were breastfed for less than 3 months. (1)Studies on asthma were less definitive. The AHRQ reported that breastfeeding for at least 3 months was calculated to provide a 27% (95% CI, 8% to 41%) reduction in the risk of asthma in children who had no family history of asthma compared with children who were not breastfed. Children who had a family history of asthma had a 40% risk (95% CI, 18% to 57%) reduction in the occurrence of asthma before 10 years of age if breastfed for 3 months compared with those not breastfed. The risk for children older than 10 years is less clear. Exclusive breastfeeding for the first 6 months is recommended by the American Academy of Pediatrics (AAP) for many reasons, including reducing the risk of allergy. Further if supplementation is necessary, an amino acid-based formula is recommended (hypoallergenic formula).The milk available in the breast after 16 weeks' gestation is called prepartum milk. When the infant delivers and is placed at the breast (or is allowed to find his or her way) to suckle, the milk is colostrum for the next few days. A gradual change from this transition milk to mature milk usually occurs by 14 days. Postpartum colostrum is called “the first immunization” because it contains high concentrations of antibodies and other infection-protective elements, including cells. Colostrum is high in total protein, low in carbohydrate, and lower in fat than mature milk. The amount of milk produced in the first 24 hours after birth is approximately 50 g, with 190 g produced by the second 24 hours, 400 g by the third 24 hours, and 1,100 g/24 hours by the fourteenth day (800 to 1,000 mL). Human milk and cow milk differ substantially in their composition (Table 2).The proteins differ in quality and quantity. In its unaltered form, cow milk contains too much protein, too much casein, too much sodium, and too much phosphorus and has too high a solute load for a human infant. Formulas have been designed to improve these issues. Cow milk does not contain any taurine, an amino acid that has high concentrations in human milk and is essential to infant brain growth. The profile of amino acids in cow milk differs significantly from human milk, especially phenylalanine and tyrosine, which are at high concentrations in cow milk and formula and contribute to problems in phenylketonuria.The effect of higher protein in infant formula recently has been questioned by investigators of the obesity epidemic. It has been suggested that a constant intake of high protein in infancy stimulates the metabolic rate and contributes to the long-term obesity of formula-fed infants. After processing, cow milk and infant formulas contain no cells, no enzymes, and no antibodies or other active protective agents and do not support the maintenance of physiologic flora of the infant's GI tract.Docosahexaenoic acid (DHA) has received considerable attention because studies in preterm infants have demonstrated improved visual acuity and auditory acuity in those fed human milk compared with those fed regular preterm formula. When DHA was added to formula, the acuity improved but did not reach the scores achieved by breastfed infants. DHA and omega-3 fatty acids derived from bacterial culture are added to many formulas, although a benefit has not been proven.Vitamin concentrations in human and cow milk are comparable, except for vitamin C, which is significantly higher in human milk (100 mg/d). Vitamins in infant formula exceed the concentrations found naturally. Vitamin D has become an important issue because the vitamin D generated in human skin from exposure to sunshine has diminished through the use of sunscreen, wearing of clothing to shade from the sun, pollution of the air by industrial waste, and migration of dark-skinned populations to climates with less sun. Pregnant women have been documented in recent decades to pass less vitamin D to the fetus, so newborns lack sufficient stores at birth. As a result, breastfed infants now are given 400 U daily from birth. Investigative work continues on the benefits of providing pregnant and lactating women with 1,000 U of vitamin D daily. Most, but not all, infant formulas contain 400 U of vitamin D in 26 to 32 oz of reconstituted formula.Vitamin K content presents an important issue for the newborn who is born with low concentrations, even when the mother receives extra doses at the time of delivery. Hemorrhagic disease of the newborn, with GI or intracranial hemorrhage and generalized bleeding, can present early or up to several weeks after birth and is due to relative deficiencies of vitamin K-dependent coagulation factors. Such deficiency has resulted in all newborns receiving 1 mg of vitamin K intramuscularly at birth, regardless of the proposed mode of feeding. If vitamin K is administered orally, multiple doses should be provided. Formula has extra vitamin K, so an infant who receives 26 to 32 oz per day of formula receives 4 mg of vitamin K orally daily. Concentrations in human milk and cow milk are lower.Neonates and infants are immunologically immature and at increased risk for infection. Such developmental immune defects are only some of the factors that place infants at greater risk of infection. In the first 6 postnatal months, phagocyte function is immature, with limited ability to migrate to the site of infection, and reserve production of phagocytes in response to infection is limited. Cell-mediated immunity develops throughout childhood. Defects are particularly apparent in the first 6 months after birth, including decreased cytokine production, decreased natural killer cell function, poor stimulation of B cells for antibody production, and limited numbers of mature functioning T cells. In addition, function of the classical and alternative pathways of complement formation and activation is decreased. Immunoglobulin (Ig) production is limited in amount and repertoire, including poor isotype switching, limited IgG subclass production, and low serum IgA concentrations through 7 to 8 years of age.Human milk not only bolsters the infant's immature immune response by providing numerous bioactive factors that dynamically affect the innate, adaptive, and mucosal immunity against specific infectious agents but also by influencing immune system development and maturation of the mucosal barrier. A very clear dose-response relationship has been documented between the amount (full [exclusive], partial, token) and duration of breastfeeding and the benefits gained by the infant and mother. (See Table 1 for the definitions.) Most bioactive factors exert their effects at the level of the mucosal immune system. Igs are the best recognized and studied bioactive components in human milk. Igs in human milk are predominantly secretory IgA, with much smaller amounts of IgM and IgG. Colostrum contains higher amounts of Igs and immunologically competent mononuclear cells than transitional or mature milk. The Igs function by binding directly to specific microbial antigens, blocking binding and adhesion to host cells, enhancing phagocytosis, and modulating local immune response. Table 3 in the online edition of this article lists specific antibodies that have been identified in human milk.The actual antibodies against specific microbial agents present in an individual woman's milk depends on her exposure and response to the particular agents. Not every mother has antibodies in her milk against every microbe. The predominant action of Igs in human milk is seen at the mucosal level of the infant's mouth, nasopharynx, and GI tract, where they bind to and block the infectious entry of microbial agents through the mucosal barrier. Although best recognized and remembered in association with “specific” protection against individual infectious agents, Igs provide only a small portion of the overall immunologic benefit of human milk.Other important individual bioactive proteins include lactoferrin, lysozyme, alpha-lactalbumin, and casein. Lactoferrin exerts its effects via iron chelation, which contributes to limiting bacterial growth, blocking adsorption and penetration of viruses and adhesion of bacteria, and enhancing intestinal cell growth and repair. Lysozyme binds to endotoxin, increases macrophage activation, and contributes to bacterial cell wall lysis. Lactalbumin transports calcium and enhances the growth of Bifidobacterium, and a modified lactalbumin (in the gut) affects immune modulation. Casein limits adhesion of bacteria and facilitates the growth of Bifidobacterium. Carbohydrates are an important nutritional component in human milk, and the specific carbohydrates lactose, oligosaccharides, and glycoconjugates act as bioactive factors. Oligosaccharides act as prebiotics, enhancing the growth of specific probiotic bacteria in breastfed infants, and both oligosaccharides and glycoconjugates bind specific microbial antigens.Lipids in the form of triglycerides, long-chain polyunsaturated fatty acids, and free fatty acids (FFAs) have a lytic effect on many viruses and are active against Giardia as well. Nucleotides, nucleosides, and nucleic acids comprise more than 15% of the nonprotein nitrogen in human milk. Nucleotides serve many crucial roles in energy metabolism, nucleic acid production, and signal transduction, processes of increased importance during the cellular activation and replication related to an active immune response. Research related to the “essential” nature of nucleotides in protection against infection has led to the addition of nucleotides to some infant formulas. Cytokines and soluble receptors of cytokines are other examples of bioactive factors that serve several functions. Cytokines can act as functional growth factors and have both inflammatory and anti-inflammatory effects in different situations.Hormones and growth factors, including erythropoietin, epidermal growth factor, insulin, insulin-like growth factor, nerve growth factor, and transforming growth factor-alpha, stimulate the growth and maturation of the GI tract and, to a degree, systemic growth. These bioactive factors are less specific than Igs, but by acting in concert with multiple factors, they provide the major portion of protective effects from human milk.The concept of immune protection without an extensive and potentially damaging inflammatory response is gaining in significance in general medicine and in breastfeeding medicine. Many of the same protective bioactive factors act at the mucosal level without stimulating a significant inflammatory response, which indirectly decreases inflammation and possible local tissue damage. Certain factors limit further inflammatory stimulation: lactoferrin blocks activation of complement, and lysozyme inhibits neutrophil chemotaxis and limits formation of toxic oxygen radicals. Various enzymes in human milk break down inflammatory molecules: catalase destroys hydrogen peroxide, histaminase destroys histamine, and arylsulfatase degrades leukotrienes. Various soluble receptors in human milk (IL-1Ra, STNF-alpha R1 and R2) bind to specific cytokines, blocking their inflammatory action.Vitamins A, C, and E, which are present in higher concentrations in human milk than in cow milk, scavenge oxygen radicals. Catalase and glutathione peroxidase as well as lactoferrin serve multiple purposes and have antioxidant properties. Prostaglandins in human milk limit superoxide production. The sum total of these anti-inflammatory effects of human milk occurring at the mucosal level limits damage to the mucosal barrier and facilitates its ongoing growth and development to further enhance human milk's protection of the infant.The concept that “normal” intestinal microflora influence the development of the local mucosal immunity and even “prime” systemic immunity is being supported by new research. Pathogen-associated molecular patterns in the microflora are recognized by toll-like receptors and may contribute to the expression of toll-like receptors on intestinal epithelial cells as well as lead to “programming” of systemic T-helper cell type 1 (TH1), TH2, and TH3-like T-cell responses. Probiotic bacteria are organisms that live symbiotically in the intestine, conferring additional benefits on the host, which include competition with pathogenic organisms, strengthened tight junctions between cells, production of antimicrobial bacteriocidins, increased mucin production, stimulated peristalsis, increased production of specific nutrients (arginine, glutamine, small-chain fatty acids), and enhanced development of the mucosal immune system.Prebiotics usually are nondigestible oligosaccharides that, after fermentation, lower the pH of the local environs and increase the amount of available FFAs. Prebiotics enhance the growth of probiotic bacteria in the intestine. Oligosaccharides are the third most common component in human milk in terms of quantity. Cow milk and formula contain less than one tenth of the oligosaccharides in human milk by weight. The microflora of breastfed infants include Lactobacillus bifidus and Bifidobacterium, which comprise up to 95% of the culturable organisms. The remaining small portion of bacteria include Streptococcus, Bacteroides, Clostridium, Micrococcus, and Enterococcus as well as Escherichia coli and other organisms in even smaller numbers. The microflora of formula-fed infants are composed primarily of gram-negative organisms (coliforms, Bacteroides, Clostridium, Enterobacter, and Enterococcus) in much larger numbers than in breastfed infants and include very small amounts of Lactobacillus and Bifidobacterium. Lactobacillus and Bifidobacterium ferment oligosaccharides, producing various acids, including FFAs, which lower the pH in the intestine and limit the growth of potential pathogens such as E coli, Bacteroides, and Staphylococcus. New molecular techniques that analyze stool by detecting ribosomal RNA sequences of microbes are expanding the understanding of GI microflora and factors influencing intestinal and immunologic development at the level of the gut. Multiple studies have suggested a protective role of specific intestinal microflora against the risk of developing necrotizing enterocolitis (NEC) in preterm and very low-birthweight infants.Despite all the evidence for the immunologic benefits of human milk and the protection afforded infants against specific organisms and separate clinical illnesses, data also document the transmission of specific infections through human milk or direct contact with an infected maternal breast. Although only a few infections are transmitted easily through human milk (human immunodeficiency virus [HIV-1], human T-lymphotrophic viruses 1 and 2 [HTLV-1 and -2], and cytomegalovirus [CMV]), these viruses are important because of their potential for causing morbidity or mortality in the infant. In addition, other infections that are uncommonly transmitted by human milk or breast contact should be considered in specific situations.Transmission of infection through human milk is exceedingly rare compared with the more common mechanisms of transmission for neonates and infants. Prenatal infection is congenital, occurring across the placenta; perinatal infection is due to passage through the birth canal; and postnatal infection occurs via airborne, droplet, or contact transmission other than with the breast. The predominant modes of transmission and the usual timing of infection are important considerations in different clinical situations. (2) Review of the considerations for transmission via human milk for selected organisms can be divided into bacterial, viral, and other. See Tables 4 and 5 in the online edition of this article for summaries of the considerations for selected bacteria and viruses.Chronic infection of the mother with HTLV-1 or -2 is considered a contraindication to breastfeeding. Studies on transmission have documented approximately a 30% transmission rate in breastfed infants, 10% rate in “mixed-feeding” infants, and 0% rate in exclusively formula-fed infants. Researchers estimate that 1 mL of human milk can contain 1,000 T cells infected with HTLV-1. Epidemiologic studies from areas of Japan that have high rates of HTLV-1 have reported significant reductions in transmission of the virus from mother to infant with avoidance of breastfeeding or limiting breastfeeding to less than 6 months' duration.HIV-1 infection in the mother is another chronic infection that can be transmitted readily via human milk to the infant. In the United States and other areas of the world where HIV perinatal transmission prevention is highly successful and safe alternatives to breastfeeding are available, acceptable, feasible, affordable, sustainable, and safe, mothers who have HIV infection have been advised not to breastfeed their infants. In areas of the world where there is an increased risk of infectious diseases, nutritional deficiencies, and significant morbidity and mortality for infants who are not breastfed and replacement feeding is not available, exclusive breastfeeding by an HIV-positive mother can afford the infant the best chance of survival. HIV DNA is detectable easily in human milk and can be categorized as cell-free and cell-associated virus. Factors associated with an increased risk of HIV transmission via breastfeeding include mixed feeding versus exclusive breastfeeding, duration of breastfeeding, maternal illness and high viral loads, lower CD4 lymphocyte counts in the mother, and mastitis or nipple lesions in the mother. Recent studies have documented that effective antiretroviral (ARV) treatment of the HIV-positive mother along with exclusive breastfeeding can lead to lower transmission rates for infants and lower mortality for both mothers and infants. Prophylactic ARV treatment of the infant along with exclusive breastfeeding also has been associated with decreased HIV transmission to the infant. Additional carefully controlled research on exclusive breastfeeding, ARV therapy, and optimizing the infant's nutrition and growth are needed before an optimal regimen can be devised.Latent CMV infection or even recent CMV infection in a breastfeeding mother is not a contraindication to breastfeeding. Postnatal CMV infection via human milk occurs readily, but viral presence is rarely, if ever, clinically significant in the term infant. In fact, breastfeeding has been described as “natural CMV immunization” in the term infant. Preterm, low-birthweight, and very low-birthweight infants are at risk for clinically significant postnatal CMV infection via breastfeeding. This postnatal infection is more likely to occur between 3 and 12 weeks postpartum, when virolactia occurs commonly. Pasteurization and freezing-thawing milk can decrease the CMV load in human milk. A reasonable protocol has been outlined for protecting susceptible infants while using human milk in nurseries that include preterm and very low-birthweight infants. (3) The protocol includes screening mothers for CMV before providing human milk to their infants, pasteurizing or freezing-thawing human milk from CMV-positive mothers before its use, and observing infants in the nursery for evidence of acute CMV infection.No prospective, controlled trials document the protective effects of such a protocol.West Nile virus (WNV) is the only other virus for which there has been evidence for transmission via human milk with any frequency. Several studies document the presence of WNV DNA as well as IgM and IgG antibodies against WNV in human milk, but no clear evidence documents clinically significant illness in infants exposed through breastfeeding by mothers who have WNV infection. The concern about viruses such as herpes simplex virus, varicella-zoster virus, vaccinia virus (smallpox vaccine virus), or variola virus (smallpox virus) is transmission through contact with skin lesions that contain the virus on the mother's nipple or breast, not through virus excreted in the milk. Temporary avoidance of breastfeeding and milk from the mother's breast that has an identified lesion due to one of these viruses may be reasonable. Prophylactic antiviral treatment for the infant along with maternal antiviral treatment usually is adequate to allow breastfeeding to continue.Viruses commonly transmitted via the respiratory route (influenza, respiratory syncytial virus, severe acute respiratory syndrome-associated coronavirus) are not transmitted through human milk. Most frequently, by the time a specific respiratory illness is diagnosed in the mother, the infant has already been exposed via respiratory secretions. There is no reason to suspend breastfeeding or the use of expressed human milk, except when severe disease in the mother prevents the ability to obtain human milk. The numerous bioactive factors (not Igs if it is early in the maternal infection) in human milk can provide the infant some ongoing protection.The concern about bacterial infections in the mother is infection of the nipple or breast (mastitis or breast abscess) that introduces the bacteria into the milk or directly into the infant's mouth. (See Table 4 for selected bacterial infections in the mother.) The risk of pulmonary tuberculosis (TB) in the mother is related to transmission via respiratory droplets, which is the same for breastfeeding or formula-fed infants in contact with their mothers. TB mastitis or TB lesions of the breast are rare. Breastfeeding or use of expressed human milk from the mother who has TB can continue once the mother is receiving appropriate antituberculous therapy and the infant is receiving isoniazid prophylactically.Staphylococcus or group A Streptococcus infection of the breast can interfere with breastfeeding. Breastfeeding or use of expressed human milk can continue when the mother is physically comfortable with the process, after a temporary suspension during the mother's initial 24 hours of effective antibacterial therapy. Prophylactic antibiotic therapy for the infant in conjunction with the maternal treatment often allays additional fear.In general, the same antibiotics used to treat a specific infection in the mother are used and are safe in the infant and in the mother's milk. Antibiotics do enter human milk, but usually in very low concentra