June 2010 Issue

Fortified Breast Milk — Vulnerable Infants Need Safe Administration of Nature’s Ideal Food
By Liesje Nieman Carney, RD, CSP, LDN
Today’s Dietitian
Vol. 12 No. 5 p 46

Suggested CDR Learning Codes: 4140, 5010, 5060, 5070; Level 3

The American Academy of Pediatrics (AAP) has deemed human milk “uniquely superior for infant feeding” and notes that Healthy People 2010 goals include having 75% of new mothers initiate breast-feeding, 50% continue breast-feeding for six months, and 25% breast-feed through one year. The AAP says that “breastfeeding should be continued for at least the first year of life and beyond for as long as mutually desired by mother and child.”1 La Leche League, the World Health Organization, and UNICEF recommend that mothers breast-feed their babies for at least two years.

A 2003 survey revealed that 10% of all U.S. infants (approximately 400,000) were exclusively breast-fed for 12 months, meaning that these infants did not receive any formula or complementary foods.2 Although breast-feeding rates did improve from 1999 to 2006, the duration and the exclusivity of breast-feeding in the United States remain slightly lower than Healthy People 2010 objectives, with 74% of mothers initiating breast-feeding, 43% providing some breast-feeding through six months, and 23% at 12 months. Exclusive breast-feeding for the first six months of life is the benchmark. Healthy People 2010 goals for exclusive breast-feeding through 3 and 6 months of age are 40% and 17%, respectively. However, only about 30% of mothers breast-feed exclusively for three months and 14% through six months.3

Breast milk is the ideal food for infants, but sometimes nature needs a little help, especially in feeding preterm infants and those who are critically ill. With infants as young as 24 weeks’ gestation now surviving, finding ways to enhance human milk through the fortification of expressed maternal breast milk or donor milk is even more important. Specific conditions warrant modifying breast milk so it can be safely administered. This article will discuss these issues.

First we need to understand breast milk composition, how premature delivery changes its composition, and why fortification may provide benefits.

Characteristics of Human Milk
Colostrum, the first “milk” produced after birth, has three times more protein than mature milk. Thick and yellow, colostrum is concentrated with immunoglobulin A and is used to “prime the gut.”4

The composition and quantity of milk changes about 48 to 72 hours after a woman gives birth. Each time the breast is emptied, the initial expression (foremilk) is thin and watery with a light blue tinge. Hindmilk, released after several minutes of nursing, has the highest fat concentration. The hindmilk fat content provides 25 to 35 kcal/100 mL more energy on average than foremilk. For comparison's sake, breast milk is generally considered to contain an average of 67 kcal/100 mL (ie, 20 kcal/oz).5

The time of day influences the quantity and the composition of breast milk. Usually the first milk expression of the day is highest in volume but lowest in fat and calories. The fat and protein content (and thus the overall caloric density) of breast milk varies for each mother and throughout the day.4

Human milk contains highly bioavailable protein, vitamins, and minerals; this is important to consider when comparing the net content of a particular nutrient in breast milk to that of an infant formula. Two characteristics of breast milk that are particularly desirable for preterm infants are DHA and arachidonic acid (ARA) and immune-enhancing properties.

DHA and ARA, long-chain polyunsaturated fatty acids that play a role in brain and eye development, are abundant in breast milk. Most infants can create DHA and ARA if they have adequate intake of essential fatty acids (EFAs) (ie, linoleic and linolenic acids). While some studies suggest that infants—particularly premature infants—have improved visual function and cognitive development with direct DHA and ARA intake, not all research supports this theory. The optimal amount of DHA and ARA fortification is yet to be determined, but since 2002, infant formula manufacturers have been adding DHA and ARA.

Breast milk has immune-enhancing properties, including antimicrobial substances that safeguard the lactating mammary gland and provide protection to the infant and constituents that promote immune system development. An in-depth discussion of this topic is beyond the scope of this article, but readers can find additional information in reference No. 6.

Specific health benefits attributed to human milk include the following:

• decreased incidence and/or severity of infectious diseases such as bacterial meningitis, bacteremia, diarrhea, respiratory tract infections, necrotizing enterocolitis (NEC), otitis media, urinary tract infection, and late-onset sepsis of premature infants;

• decreased postneonatal infant mortality;

• enhanced performance on cognitive/developmental tests;

• improved visual acuity;

• protection against obesity, Crohn’s disease, lymphoma, leukemia, and diabetes; and

• faster gastric emptying and improved tolerance of feedings.

Presuming that an infant is drinking sufficient volume daily (at least 160 mL/kg) and that the milk supply is consistent, exclusively feeding breast milk from birth through the age of 6 months meets a typical infant’s nutrient needs, excluding vitamin D. In 2008, the AAP recommended that all infants have a daily intake of 400 IU of vitamin D for the first few days of life. In response, most pediatricians are recommending supplementation with 400 IU of vitamin D daily either as drops or an infant multivitamin. 

Besides volume, one factor that determines how long exclusive breast-feeding will meet 100% of an infant’s nutrient needs is the infant’s nutrient store status. Premature birth (minimal stores of nutrients) and excessive vitamin/mineral losses due to disease or surgery determine when the nutrient stores will be exhausted.

For most infants, iron and zinc are the limiting factors in determining adequacy of exclusive breast milk feedings. Complementary foods rich in iron and zinc should be introduced by the age of 6 months. Premature infants are born with far less stored calcium, iron, and zinc than term infants. Thus, premature infants require higher intakes of these nutrients, which can be provided by fortifying breast milk. Fortification will be discussed in depth later in this article.

The quality of breast milk is relatively stable. The lactose content of human milk is very high and is unaffected by maternal diet changes. Breast milk’s water-soluble vitamin content varies with maternal diet. Fat-soluble vitamins are not as affected by diet as are water-soluble vitamins, but the breast milk may reflect some changes in maternal intake.7 The maternal diet influences the fat composition but not the total fat content of breast milk.

The maternal diet generally does not influence the mineral content of breast milk. Studies suggest that zinc concentrations in human milk are relatively resistant to maternal zinc status and diet.2 But researchers have observed variations in the zinc content of breast milk among different women. When they investigated further, they found that women have similar zinc concentrations in their milk at comparable postpartum stages. There is a threefold to fourfold zinc concentration decline in milk between two weeks and five months postpartum.2

Milk Fortification
Breast milk provides the best nourishment for healthy term infants born to healthy mothers, and human milk is the preferred feeding for infants born prematurely because of its immune-enhancing properties, improved developmental outcomes, and decreased risk of death and NEC.8 “Preterm milk” is roughly equal to mature milk in calories and fat; has more protein, medium-chain triglycerides (MCTs), and sodium; and has less lactose.

So why fortify breast milk? Simply, unfortified milk provides inadequate protein, sodium, calcium, and phosphorus to meet preterm infants’ needs.9 When an infant is born prematurely, the mother’s breast milk has a different nutritional composition for the first two to four weeks of lacation—nature’s way of meeting the premature infant’s unique nutritional needs. Unfortunately, in most cases the preterm breast milk will not be available long enough to see the infant through 40 weeks’ gestation (ie, full term). In donor and preterm milk, protein content decline consistently from 2 g/100 mL at the first week of life to 1g/100 mL at six months.5 The mean protein concentration of premature milk in the second week of lactation is 1.5 g/dL (2.25 g/100 kcal).10 Exclusive feeding of unfortified breast milk in premature infants has been associated with poor growth and nutritional deficits.11 A meta-analysis published in 2004 concludes that premature infants receiving fortified human milk demonstrated greater short-term weight gain, length gain, and head growth. However, the analysis revealed no long-term advantage in terms of growth, neurodevelopmental outcomes, or bone mineral content.12

O’Connor and colleagues report that preterm infants who received fortified breast milk experienced slower growth rates but similar developmental outcomes compared with infants fed nutrient-enriched premature formulas.13 Since slow growth is often an indication of inadequate nutrition and has the potential for neurological impairment, Arslanoglu concludes that “further refinement of human milk fortification models is warranted.”9 In addition, to achieve postnatal growth rates similar to intrauterine growth, protein intake needs to be higher than standard fortification can provide.

Initiating milk fortification varies based on an infant’s intake. Fortification often begins when infants tolerate feedings of unfortified breast milk at 100 to 150 mL/kg/day. Many clinicians begin fortification when infants tolerate feedings at 100 mL/kg/day. Informal reports have suggested that more aggressive fortification—starting when infants tolerate feedings at 50 mL/kg/day—is well tolerated.

For infants to achieve optimal nutrient intake (ie, calories, protein, vitamins, minerals), a minimum intake of 150 mL/kg/day with preterm milk fortified to 24 kcal/oz is required. Abbott Nutrition and Mead Johnson Nutrition recommend against exceeding 24 kcal/oz concentration (ie, 1 packet per 25 mL) with their human milk fortifiers (HMFs). However, Prolacta Bioscience has created human milk-based fortifiers specifically indicated for concentrating up to 30 kcal/oz.

The accompanying table provides a summary of commercially available products.  

Issues With HMFs
In general, HMFs are indicated until an infant reaches 3.6 kg; however, there are some exceptions to this recommendation, one of which is severe osteopenia. Care must be taken not to oversupplement. A daily intake of greater than 25 packets of powdered HMF greatly increases the risk of excessive vitamin A and D intake.

When deciding which HMF product to use, one must weigh the risks vs. the benefits of using powdered products since they are not sterile. Premature infants are immune compromised; there have been reports of deaths due to bacterial infections that were traced back to powdered formulas. Prolacta Bioscience manufactures the only liquid HMF products available in the United States, but these products may be cost prohibitive. The company will provide cost analyses for institutions interested in adding these products to the hospital formulary.

Some infants may exhibit gassiness and/or bloating and general intolerance for cow’s milk-based HMFs. Historically, there were no alternative HMF products available that were specifically formulated to meet premature infants’ nutritional needs, and thus breast milk was fortified with protein hydrolysate or amino acid-based formulas intended for term infants. Infant formulas designed for term infants do not have calcium and phosphorus levels comparable with HMF products, and this feeding practice is of particular concern due to the increased propensity for premature infants to develop osteopenia.

Using exclusive human milk feedings (maternal breast milk fortified with human milk-based fortifiers) is associated with lower rates of NEC compared with breast milk fortified with cow’s milk-based products.14 Also, the individualized fortification of human milk is a better strategy to meet premature infants’ nutritional needs.

Two types of individualized fortification have been described: targeted fortification and adjustable fortification.9 The former involves periodic milk analysis, with fortification to reach a targeted protein intake. In the latter method, blood urea nitrogen is monitored as an approximation of an infant’s metabolic response and protein intake is adjusted as needed. In comparing the two methods, adjustable fortification seems to be a more practical and effective strategy to support growth similar to intrauterine velocity.9

Donor Breast Milk
Not all mothers are willing or able to provide sufficient breast milk for their infants. Infant hospitalization is particularly stressful for parents, and stress adversely affects maternal milk supply. In the absence of an infant’s own mother’s milk, donor milk offers many of the benefits of maternal breast milk, including an optimal nutrition profile, easy digestibility, and immunologic protection. Human milk also contains growth factors that can protect immature tissue; promote maturation, particularly in the gastrointestinal tract; and promote healing of tissue damaged by infection.

Donor milk may be indicated for the following reasons:

• prematurity;

• allergies;

• feeding/formula intolerance;

• immunologic deficiencies;

• postoperative nutrition; or

• infectious diseases.

Obtaining donated milk outside the hospital setting is generally impractical due to the cost. However, using donor milk in neonatal ICUs can save thousands of dollars by decreasing the number of days on parenteral nutrition support, the length of stay, and the rates of infection and NEC.

Banked donor milk is generally provided by mothers of term infants who donate for a multitude of reasons: high-volume production of expressed breast milk exceeding their own infants’ needs, infant death, or medical contraindications (eg, galactosemia). Donor milk banks receive milk from lactating mothers who have been carefully screened for health behaviors and communicable diseases, similar to the methods used to screen blood donors. Milk bank donors must be nonsmokers, not regularly consume any medication (including mega-vitamins), and not consume excluded medications or alcohol within the specified exclusion period.

Donated milk is frozen and transported to the milk bank. After it has thawed, milk from several donors is pooled and then pasteurized to kill any bacteria or viruses. The milk is processed and then refrozen. Before dissemination, all milk is cultured to prove there is no bacteria growth. Milk is shipped frozen by overnight express to hospitals and to individual recipients at their homes.

Because donor breast milk undergoes pasteurization, many people express concern that the benefits inherent to human milk will be diminished. According to Wight, “Pasteurization does affect some of the nutritional and immunologic components of human milk, but many immunoglobulins, enzymes, hormones, and growth factors are unchanged or minimally decreased.”15 The use of donor breast milk has not been studied as extensively as feeding maternal breast milk; however, donor breast milk seems to be the next best choice for feeding when a mother is unable or unwilling to breast-feed or pump.

Specific Disease States
Historically, breast milk has been considered to be contraindicated for certain disease states because of its macronutrient composition. Some clinicians have begun allowing human milk administration to some extent in a handful of diseases, but this practice has not yet become the standard of care. Scientists have much to learn from randomized, controlled clinical trials to document long-term effects of treatments and evaluate whether the interventions significantly affect outcomes.

However, breast milk is now considered appropriate in several diseases, including chylothorax, a type of pleural effusion that involves the presence of chyle (ie, lymphatic fluid) in the pleural space caused by thoracic duct leakage. The primary treatment is a diet restricted in long-chain fatty acids (LCFAs). However, MCTs do not cause an increase in chylous effusions because they are metabolized differently than LCFAs.

Until recently, infants affected by conditions such as chylothorax were not given breast milk due to its high LCFA content. Instead, they were given a formula rich in MCTs. There are several commercial formula products available in this category, including Enfaport LIPIL (Mead Johnson Nutrition), Portagen (Mead Johnson Nutrition), Monogen (Nutricia of North America), and Lipistart (Vitaflo). Enfaport LIPIL is the only MCT-rich formula indicated for infant use; the other formulas are indicated for those aged 1 and older.

Before Enfaport LIPIL became available in 2009, the other products were given to infants “off label” because there was no comparable formula indicated for that age group. Enfaport LIPIL is also the only MCT-rich formula available in liquid form, which is preferred since powdered formulas are not sterile, as previously mentioned.

Mothers are generally encouraged to pump and store their breast milk with the hope that the infant can transition back to breast milk after the chylothorax or chylous effusion has resolved. Unfortunately, this may take many months. Often mothers become discouraged and eventually discontinue pumping.

A recent case report described the successful use of “skim breast milk” in an infant with chylothorax.16 It is possible to use a refrigerated centrifuge to spin off the fat from breast milk, resulting in milk that is virtually fat free. This method is, however, quite cost prohibitive in the hospital, and it is unrealistic to expect a caregiver to execute this at home. Lessen describes an alternate method involving the following steps:

1. Leave expressed breast milk undisturbed in the refrigerator for eight to 12 hours, allowing the fat to congeal and rise to the top.

2. Use a syringe and feeding tube to siphon out the fat-free portion of the milk, leaving the fat layer in the container.

3. Refrigerate milk again for several hours.

4. Repeat steps 2 and 3 until there is no visible fat accumulation at the top of the container.

This is only a summary of this method; the original publication provides more details.16

Removing the fat manually does not guarantee fat-free breast milk, but most facilities are able to use the creamatocrit method to evaluate fat content and caloric density.17 An in-depth description of this process is beyond the scope of this article.

Fat provides approximately one half of the calories in human milk.16 After the skimmed breast milk has reached an “acceptable” level of fat content (depending on the opinion of the prescriber), the milk provides only about 10 kcal/oz. Generally, a high-MCT formula is used to fortify the human milk to provide adequate total fat and calories.

When administering MCT-rich formulas, the provision of EFA supplementation is necessary to prevent deficiency. EFAs include linoleic and alpha-linolenic acids, both of which are LCFAs and cannot be synthesized endogenously. Adequate EFA intake is generally regarded as a minimum of 3% to 3.5% of calories from linoleic acid and 0.5% to 1% of calories from alpha-linolenic acid. Of note, premature infants often require higher intakes of EFA to prevent EFA deficiency (4% to 5% of calories from linoleic acid and 1% of calories from alpha-linolenic acid.) Commonly found oils contain varying amounts of linoleic and alpha-linolenic acids. The goal is to achieve adequate EFA intake using the least amount of LCFA possible; this can be accomplished effectively by using a combination of walnut oil and flaxseed oil.    

Metabolic Disorders
Infants diagnosed with inborn errors of metabolism must be treated with specifically designed dietary regimens, with the ultimate goal of limiting the substrate(s) that the body cannot adequately metabolize. In phenylketonuria (PKU), the offending substrate is phenylalanine (PHE), an essential amino acid. As soon as PKU is diagnosed, an individualized diet is prescribed, combining a PHE-free formula with breast milk or a standard infant formula.

If a mother decides she wants to breast-feed, the goal should be to support her in providing breast milk to her infant. Some clinicians may encourage mothers to pump and feed the expressed breast milk to the infant in specific quantities to more accurately measure an infant’s PHE intake. Although it can be a tricky undertaking, breast-feeding can be safely incorporated into the treatment plan for most infants with PKU.

Clinicians prescribing and adjusting the diet can utilize several strategies for safely breast-feeding an infant with PKU. One method is to feed a specified volume of PHE-free formula prior to each breast-feeding to offset the volume of breast milk that the infant will drink. This strategy is based on the assumption that an infant will drink a predictable amount of total volume daily.18

This method requires the mother to pump after each breast-feeding attempt because the infant will not fully empty the breast. This also means that the infant likely does not receive much hindmilk during the breast-feeding, so the total caloric intake may be adversely affected.

A second, more progressive approach to breast-feeding infants with PKU involves alternating feedings between breast-feeding and PHE-free formula via bottle. The number of daily breast-feeding attempts is adapted to the plasma PHE concentrations. At each feeding (either bottle or breast-feeding), the child is allowed to drink until satiety. This new approach is more convenient for parents. Also, the infant will be able to empty the breast, drinking not only foremilk but also hindmilk. In 2003, researchers evaluated this method in an intervention study, and the infants following this feeding pattern had adequate metabolic control comparable to the control group.19

Conclusion
Although unadulterated breast milk is the optimal source of nutrition for most infants, there are some conditions that warrant additional consideration.

— Liesje Nieman Carney, RD, CSP, LDN, is a clinical dietitian IV and publication specialist at the Children’s Hospital of Philadelphia. Her areas of clinical interest include neonatal intensive care, pediatric nutrition support, and inborn errors of metabolism. She is active with the Pediatric Nutrition Dietetic Practice Group’s executive committee.

 

Learning Objectives
After completing this continuing education exercise, the student should be able to:

1. List the unique characteristics of human milk.

2. Discuss the short- and long-term benefits of infants consuming human milk.

3. Understand the rationale and strategies for fortifying breast milk.

4. Describe the methods used to manipulate breast milk so that it can be administered safely in specific disease states.

 

Examination
1. Which of the following are health benefits of human milk?
a. Improved visual acuity
b. Decreased incidence of necrotizing enterocolitis
c. Decreased incidence of otitis media
d. All of the above

2. Colostrum is a concentrated source of:
a. fat.
b. carbohydrates.
c. immunoglobulin A.
d. hindmilk.

3. The usual caloric concentration of unfortified, mature breast milk is:
a. 30 kcal/oz.
b. 25 kcal/oz.
c. 20 kcal/oz.
d. 10 kcal/oz.

4. When an infant is born prematurely, the mother’s breast milk is considered to be “preterm” for how long?
a. Three to five days
b. Six to 10 weeks
c. One to two weeks
d. Two to four weeks

5. The quality of breast milk is relatively stable.
a. True
b. False

6. What is the recommended duration of exclusive breast-feeding?
a. 12 months
b. First six months of life
c. Four months
d. 24 months

7. Feeding unfortified human milk to a premature infant provides inadequate amounts of which nutrients?
a. Protein, sodium, calcium, and phosphorus
b. Zinc, calcium, fat, and calories
c. Magnesium, potassium, calcium, and phosphorus
d. Protein, zinc, selenium, and medium-chain triglycerides

8. According to the manufacturers of cow’s milk-based powdered human milk fortifiers (HMFs), breast milk should be fortified to a maximum caloric concentration of:
a. 20 kcal/oz.
b. 22 kcal/oz.
c. 24 kcal/oz.
d. 30 kcal/oz.

9. HMFs are indicated for infants up to what weight?
a. 4 kg
b. 2 kg
c. 2.5 kg
d. 3.6 kg

10. What are the benefits of providing “skim breast milk” to infants with chylothorax?
a. Low long-chain fatty acid intake
b. Immune-enhancing properties
c. Formula use can be avoided
d. Both a and b

 

References
1. Gartner LM, Morton J, Lawrence RA, et al. Breastfeeding and the use of human milk. Pediatrics. 2005;115(2):496-506.

2. Krebs NF, Hambidge KM. Complementary feeding: Clinically relevant factors affecting timing and composition. Am J Clin Nutr. 2007;85(2):639S-645S.

3. Centers for Disease Control and Prevention. Breastfeeding among U.S. children born 1999-2006, CDC national immunization survey. Last updated March 16, 2010. Available at: http://www.cdc.gov/breastfeeding/data/nis_data/index.htm

4. Spatz DL. State of the science: Use of human milk and breast-feeding for vulnerable infants. J Perinat Neonatal Nurs. 2006;20(1):51-55.

5. Saarela T, Kokkonen J, Koivisto M. Macronutrient and energy contents of human milk fractions during the first six months of lactation. Acta Paediatr. 2005;94(9):1176-1181.

6. Field CJ. The immunological components of human milk and their effect on immune development in infants. J Nutr. 2005;135:1-4.

7. Carney G. Complementary nutrition during lactation. Building Block for Life. 2008;32(1):1-5.

8. Arslanoglu S, Moro GE, Ziegler EE. Optimization of human milk fortification for preterm infants: New concepts and recommendations. J Perinat Med. 2010;[Epub ahead of print].

9. Schanler RJ. The use of human milk for premature infants. Pediatr Clin North Am. 2001;48(1):207-219.

10. Lemons JA, Moye L, Hall D, Simmons M. Differences in the composition of preterm and term human milk during early lactation. Pediatr Res. 1982;16(2):113-117.

11. Kashyap S, Schulze KF, Forsyth M. Growth, nutrient retention, and metabolic response of low-birth-weight infants fed supplemented and unsupplemented preterm human milk. Am J Clin Nutr. 1990;52(2):254-262.

12. Kuschel CA, Harding JE. Multicomponent fortified human milk for promoting growth in preterm infants. Cochrane Database Syst Rev. 2004;(1):CD000343.

13. O’Connor DL, Jacobs J, Hall R, et al. Growth and development of premature infants fed predominantly human milk, predominantly premature infant formula, or a combination of human milk and premature infant formula. J Pediatr Gastroenterol Nutr. 2003;37(4):437-446.

14. Sullivan S, Schanler RJ, Kim JH, et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr. 2010;156(4):562-567.e1.

15. Wight NE. Donor human milk for preterm infants. J Perinatol. 2001;21(4):249-254.

16. Lessen R. Use of skim breast milk for an infant with chylothorax. ICAN: Infant, Child, & Adolescent Nutrition. 2009;1(6):303-310.

17. Lucas A, Gibbs JA, Lyster RL, Baum JD. Creamatocrit: Simple clinical technique for estimating fat concentration and energy value of human milk. Br Med J. 1978;1(6119):1018-1020.

18. Greve LC, Wheeler MD, Green-Burgeson DK, Zorn EM. Breast-feeding in the management of the newborn with phenylketonuria: A practical approach to dietary therapy. J Am Diet Assoc.1994;94(3):305-309.

19. van Rijn M, Bekhof J, Dijkstra T, et al. A different approach to breast-feeding of the infant with phenylketonuria. Eur J Pediatr. 2003;162(5):323-326.

 

Resources
• Centers for Disease Control and Prevention: www.cdc.gov/breastfeeding

• Human Milk Banking Association of North America: www.hmbana.org

• Iowa Neonatology Handbook: Feeding Guidelines for the Use of Human Milk Fortifier in the Neonatal Intensive Care Unit by Susan Carlson RD, CSP, LD; Beth Wojcik RD, LD; and Jonathan Klein, MD (www.uihealthcare.com/depts/med/pediatrics/iowaneonatology
handbook/feeding/guidelineshumanmilk.html)

• La Leche League: www.llli.org, www.lllusa.org

 

Suggested Reading
• Ahring K, Bélanger-Quintana A, Dokoupil K, et al. Dietary management practices in phenylketonuria across European centres. Clin Nutr. 2009;28(3):231-236.

• Barrett Reis B, Hall RT, Schanler RJ, et al. Enhanced growth of preterm infants fed a new powdered human milk fortifier: A randomized, controlled trial. Pediatrics. 2000;106(3):581-588.

• Boyd CA, Quigley MA, Brocklehurst P. Donor breast milk versus infant formula for preterm infants: Systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2007;92(3):F169-175.

• Feillet F, Agostoni C. Nutritional issues in treating phenylketonuria. J Inherit Metab Dis. 2010;[Epub ahead of print].

• Gregory K. Update on nutrition for preterm and full-term infants. J Obstet Gynecol Neonatal Nurs. 2005;34(1):98-108

• Hanson LA, Korotkova M. The role of breastfeeding in the prevention of neonatal infection. Semin Neonatol. 2002;7(4):275-281.

• Henderson G, Anthony MY, McGuire W. Formula milk versus maternal breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev. 2007;(4):CD002972.

• Koletzko B, Lien E, Agostoni C, et al. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: Review of current knowledge and concensus recommendations. J Perinat Med. 2008;36(1):5-14.

• Quigley MA, Henderson G, Anthony MY, McGuire W. Formula milk versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev. 2007;(4):CD002971.

• Wagner CL, Greer FR, American Academy of Pediatrics Section on Breastfeeding, American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142-1152.

 

Commercially Available Human Milk Fortifiers
Product	Similac Human Milk Fortifier (Abbott Nutrition)1	Enfamil Human Milk Fortifier (Mead Johnson Nutrition)2	Prolact+4 H2MF (Prolacta Bioscience)3
Indication	For low–birth-weight infants until they reach a weight of 3,600 g	For breast-fed babies who were born early or at a low birth weight	Formulated to fortify breast milk to a minimum of 24 kcal/oz
Packaging	0.9-g packet (powder)	0.71-g packet (powder)	10 mL and 20 mL (liquid)
Preparation	1 packet/50 mL breast milk yields 22 kcal/oz; 1 packet/25 mL breast milk yields 24 kcal/oz	1 packet/50 mL breast milk yields 22 kcal/oz; 1 packet/25 mL breast milk yields 24 kcal/oz	Mix 10 mL bottle with 40 mL breast milk, yields 24 kcal/oz
Protein source	Cow’s milk	Cow’s milk	Human milk
Nutrients	Per serving (1 packet)	Per 4 packets	Per 10 mL
Calories	3.5	14	14.6
Protein	0.25 g	1.1 g	0.6 g
Fat	0.09 g	1 g	0.9 g
Vitamin A	155 IU	950 IU	30.6 IU
Vitamin D	30 IU	150 IU	13 IU
Vitamin E	0.8 IU	4.6 IU	0.2 IU
Calcium	29.25 mg (1.46 mEq)	90 mg	54.2 mg
Phosphorus	16.8 mg (0.54 mEq)	50 mg	31 mg
Iron	0.08 mg	1.44 mg	0.1 mg
Zinc	0.25 mg	0.72 mg	0.3 mg
Miscellaneous Characteristics	Low iron level provides flexibility to add iron as needed; additional iron should be supplied from other sources		Additional vitamins may be required; the first and only human milk fortifier made from concentrated 100% human milk; pasteurized product
Potential Renal Solute Load	2.8 mOsm	9.7 mOsm/100mL (per 4 packets)	N/A

1. http://abbottnutrition.com/Products/similac-human-milk-fortifier
2. www.mjn.com/app/iwp/hcp2/content2.do?dm=mj&id=/HCP_Home2/Product
Information/hcpProducts/hcpInfants/hcpHMF&iwpst=MJN&ls=0&csred=1&r=3449494765
3. www.prolacta.com/fortifier.php