Breastfeeding In The Preterm Infant

Brady A. Kerr, M.D. and James Kirk, D.O.

 

Introduction

Universal breastfeeding has been a stated goal of the American Academy of Pediatrics, as well as the World Health Organization. Although human milk is generally accepted as the gold standard for the feeding of term infants, its use in preterm infants has been more controversial. As health care professionals, we must strive to maximize the nutritional and developmental outcomes of preterm infants. This article reviews the advantages of breastfeeding in general, as well as the nutritional needs of premature infants and the use of human milk fortification to meet those demands.

Benefits Of Breast Feeding

The catch phrase "breast is best" has been extensively researched over the last twenty years. A large body of evidence clearly supports that breastfeeding enhances host defense mechanisms, improves neurodevelopmental outcomes, and may even have long-term protective properties against chronic diseases in children. In addition, breast milk enhances development of the gastrointestinal system and promotes maternal-infant bonding. In regards to host defenses, breast fed infants have decreased rates of necrotizing enterocolitis compared to formula fed infants.1 In addition, breastfed infants have been shown to have a lower prevalence of various infections compared to exclusively formula fed infants.2 Finally, breastfed infants have been observed to excrete greater amounts of IgA and lactoferrin in their feces and urine.3,4 Such results suggest that human milk may improve infants' host defenses through local actions in the gastrointestinal and urinary tracts.5

With regards to neurodevelopment, some studies have suggested that preterm breastfed infants have higher intelligence quotient (IQ) scores compared to formula-fed infants.6 Lucas et al followed a cohort of 300 preterm infants to the age of 7.5-8 years and found that breastfed infants had an 8.3 point advantage compared to their nonbreastfed counterparts using an abbreviated version of the Weschler Intelligence Scale for Children. Such data, while providing strong support for breastfeeding, should be interpreted cautiously. There are a variety of other variables influencing IQ scores which are difficult to quantify, such as parental attributes, genetic potential, and motivational behavior patterns. Other groups have studied brainstem maturation in preterm infants as a function of brainstem auditory evoked responses (BAERs) and have shown that breastfed infants have accelerated brainstem maturation compared with formula-fed infants.7 Breastfed preterm infants have also been shown to have a decreased incidence and severity of retinopathy of prematurity versus formula-fed infants.8 Breast milk has a high quantity of polyunsaturated fats (PUFAs),9 which have antioxidant activity, and may protect retinal membranes.8

In addition to its beneficial effects on host defense and neurodevelopment, breastfeeding or the lack thereof may influence the risk for certain chronic diseases of childhood.10 Numerous studies have considered whether artificial feeding increases the risk for insulin dependent diabetes mellitus (IDDM), celiac disease, childhood cancer, and inflammatory bowel disease. The relationship between IDDM and infant feeding practices has been studied the most extensively with over 100 articles published. Many studies have explored exposure to cow's milk protein as a potential environmental trigger for IDDM.10

Compared to the possible influence of breast milk on childhood diseases, the influence of breast milk on the gastrointestinal tract is more widely accepted. Preterm infants are often given small volumes of human milk during the early days of life. Numerous animal studies have demonstrated that such low volume feeds promote a more mature motility pattern, a lower incidence of cholestasis, and help maintain mucosal integrity.11 Finally, breastfeeding establishes skin-to-skin contact and facilitates infant-maternal bonding.

Nutritional Needs Of The Preterm Infant

Just as pediatric patients are not "little adults," the preterm infant clearly has increased nutritional needs compared to the infant born at term. Furthermore, extremely low birth weight (ELBW) infants (those who weigh <1000g at birth) have even greater metabolic demands. Traditionally, nutritional support of ELBW infants has targeted establishing fetal growth by addressing the changing nutritional requirements of these infants. Despite the many medical advances in the past twenty years which have improved the survival of preterms infants, their postnatal growth continues to lag.12 In fact, recent studies of postnatal growth in large numbers of infants cared for in modern NICU's have shown a common difficulty in achieving intrauterine growth rates, but significant internursery variability.37 Growth was most accelerated in those units that instituted enteral feedings early and advanced total nutrition aggressively.

Currently, little direct evidence exists in human fetuses for the specific composition and amount of nutrients needed to support normal fetal growth.13 Many experiments have attempted to provide inferential data. For example, studies with fetal sheep have shown at late second and early third trimester ovine fetuses use 8 to 10 mg/kg/min of glucose. This rate is approximately the maximum rate of glucose that is tolerated by ELBW infants at comparable gestational ages.14 With respect to basal energy requirements, other studies have determined that ovine fetuses require 50 kcal/kg/day, a need similar to that of preterm human neonates.15,16

Amino Acids

The overall quantity as well as quality of amino acids is important to consider to achieve optimal growth. The ELBW infant is estimated to require 4.0 g/kg/d of protein or amino acids.17 Even providing intravenous amino acids at rate of 1.1 to 1.5g/kg/day provides a slightly positive protein balance and promotes net protein anabolism by sparing endogenous protein stores.18 In addition to protein quantity, protein quality is essential in order to maximize protein utilization. An adequate intake of essential amino acids (e.g. tyrosine, cysteine, and taurine) is required.19 Furthermore, a sufficient amount of nonessential amino acids is needed to prevent diversion of the essential amino acids to the synthesis of nonessential amino acids.13

Lipids

Dietary fat is an important determinant of membrane lipid composition and central nervous system development. In both human milk and formulas, lipids comprise about 50% of the total energy and contain the essential fatty acids, linolenic acid and linoleic acid.13 However, ELBW infants usually receive their dietary fat via parenteral lipid emulsions. Such emulsions may have limited or delayed use because of concerns that lipid intolerance in premature neonates may have adverse effects, such as impaired oxygenation, increased risk of lung disease, impaired immune function, and increased free bilirubin levels.13 Despite these concerns, clinical studies have shown that infusion of lipid at rates up to 3 g/kg/day does not necessarily increase plasma concentrations of free fatty acids or free bilirubin.20

Glucose

In addition to amino acids and lipids, preterm infants also have increased glucose requirements. In term infants, a glucose infusion rate of 3 to 4 mg/kg/min is sufficient to prevent hypoglycemia.21 ELBW infants often require 6 to 10 mg/kg/min to maintain adequate glucose levels.22 ELBW infants may also have a lower threshold for defining hypoglycemia. In term infants, less than 40 mg/dL is commonly accepted as the threshold for hypoglycemia. Cordocentesis studies of normal human fetuses over the second half of gestation have demonstrated that fetal glucose concentration is > 50 to 55 mg/dL.23 Slightly lower glucose levels from these have been implicated with an increased risk of motor and developmental delay.24 Thus, 50 to 55 mg/dL may be a more appropriate lower boundary of adequate blood glucose levels in ELBW infants.

Trace Elements

The importance of a variety of trace elements in the preterm infant remains unknown. Currently, iron, zinc, copper, and selenium all have been established as vital trace elements in the ELBW infant. Dietary zinc has been shown to improve growth and motor development, and selenium is an important antioxidant.13

Human Milk Fortification

Nutritional Concerns with Unfortified Human Milk

Premature infants fed exclusively unfortified human milk have been associated with poor rates of growth and nutritional deficits during and beyond hospitalization.25 Many reasons may explain why unfortified human milk may not provide adequate nutrients to meet the demands of premature infants. First, there is a large variation in the protein and fat content of preterm human milk.25 The protein content of human milk decreases throughout lactation, thus providing varying amounts of nutrients.26 Also, the fat content of human milk varies from early to late lactation, throughout the day, from mother to mother, and within a single milk expression.27,28 Hindmilk may have up to threefold greater fat than foremilk.29 Further variations in the fat content of human milk can occur as a result of the collecting, mixing, or storing of the milk during which the fat may become separated from the milk.25

In contrast to protein and fat content, calcium and phosphorous levels do not change substantially through lactation. However, the levels of these nutrients are not sufficient to fulfill the demands of premature infants.25

Fortified Human Milk

The nutritional deficits of preterm human milk can be corrected through appropriate supplementation via fortifiers. Essentially, human milk fortifiers can be broken into two groups: liquid fortifiers and powder fortifiers. Most fortifiers are powdered preparations containing protein, carbohydrate, calcium, phosphorous, magnesium, and sodium. Currently, no fortifier provides sufficient amounts of iron to meet the needs of the premature infant.25 Both types are mixed with the mother's milk.

Below is a summary comparison of commercially available human milk fortifiers.

Powdered human milk fortifiers have some advantages compared to the liquid fortifiers. Powdered fortifiers have higher a protein content and net protein retention. Calcium, phosphorous, and zinc contents are also higher compared to the liquid fortifiers. Also, powdered fortifiers have the advantage of not diluting the mother's milk. Liquid fortifiers are best reserved for cases in which the mother is unable to produce an adequate supply of milk to meet her infant's needs. A common practice is to feed powder fortified human milk for as many feedings as possible, then switch to preterm infant formula for the remaining feedings.25

Even though fortified human milk provides the benefits associated with human milk and corrects some of the nutritional deficits found in unfortified milk, it still results in lower growth rates than does preterm infant formula.30 However, this slower rate of growth does not seem to be associated with poorer nutrition.25

Feeding Regimens

A variety of feeding regimens exist for fortified human milk in premature infants. One option is to begin fortifying the human milk when the infant reaches an enteral intake of 100 mL/kg/day.31 Next, the total volume of feeds is maintained while the concentration of the feeds is gradually increased over 2 to 4 days with the addition of the fortifier. One packet of powdered fortifier per 25 ml of breast milk increases the caloric density from 20 to approximately 24 kcal/oz.38 This method of fortification provides additional protein, calcium, phosphorous, zinc, and cooper which may be deficient in unfortified breast milk. No additional vitamin supplementation is required, except iron, which maybe initiated once complete enteral feeding is reached.25

Finally, the volume of the feeds is advanced daily to achieve a body weight gain of 15 g/kg/day.31 Caution should be exercised when increasing feeds as rapid advancement may overwhelm the adaptive capabilities of the gastrointestinal tract and cause feeding intolerance.38

The fortified human milk is prepared daily and stored at refrigerator temperature. For ELBW infants, the milk should be stored in small aliquots for thawing or warming of small feeding volumes in order to minimize wasting the maternal milk supply.32

Contraindications To Breastfeeding

Despite a strong body of evidence for both breastfeeding in general and the feeding of fortified human milk to breast fed infants, there are a number of situations in which breast feeding could prove harmful. First, there are a variety of infectious diseases which place infants at risk during breastfeeding, although maternal infections are not a contraindication to breastfeeding in most cases.33 For example, mothers with the "common cold" can breast feed without any fear of detrimental effects on their infants.

One infectious disease that is clearly a contraindication to breastfeeding is human immunodeficiency virus (HIV), which can be transmitted through breast milk.34 In addition, in developed countries human T-cell lymphotrophic virus, and cytomegalovirus (CMV) all can be passed to infants during breastfeeding. Recent studies of CMV transmission via breast milk have found that CMV seropositive mothers excrete an extremely high degree of CMV in their breast milk after delivery of a small preterm infant.35 Herpes simplex virus is not a contraindication to breastfeeding unless the mother has active herpetic lesions on her breast. With regards to maternal varicella-zoster infection, if no varicella-zoster virus (VZV) lesions involve the breast and the infant has received varicella zoster immuneglobulin (VZIG), breastfeeding can resume when the mother is no longer infectious.36

A variety of other contraindications to breastfeeding may exist such as active tuberculosis (TB) infection, galactosemia, and mothers with unusual dietary practices (such as strictly vegatarian diets). Most prescribed and over-the-counter medications are safe for breastfeeding infants; however, some medications are contraindicated for breastfeeding including radioactive isotopes, antimetabolites, and cancer chemotherapy agents. Finally, mothers who use illicit drugs, such as cocaine, should not breastfeed.

Conclusion

Clearly, the nutritional needs of preterm infants differ substantially from the requirements of term babies. Fortified human milk is an appropriate nutritional source for preterm infants that has advantages compared to either preterm formula or unfortified human milk. Current studies are continuing to investigate the constituents of human milk fortifiers, as well as feeding practices that promote optimal growth and development of the ELBW infant.

References

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December, 2001/ Jacksonville Medicine

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