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Challenges in the practice of human milk nutrition in the neonatal intensive care unit
EHD-03840; No of Pages 4 Early Human Development xxx (2013) xxx–xxx
Contents lists available at ScienceDirect
Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
Challenges in the practice of human milk nutrition in the neonatal intensive care unit Jae H. Kim ⁎, Christina S. Chan, Yvonne E. Vaucher, Lisa M. Stellwagen University of California, San Diego, 200 West Arbor Dr. MPF 1140, San Diego, CA 92103-8774, USA
a r t i c l e
i n f o
Available online xxxx
a b s t r a c t The use of human milk for preterm infants has increased over the past decade reflecting an improved awareness of the benefits of human milk. Inherent in this paradigm shift is the recognition that human milk is a living tissue; full of immune cells, probiotics and hundreds of compounds that confer bioactivity and immune protective properties. Together these factors deliver a powerful effect in reducing clinical morbidities such as necrotizing enterocolitis and sepsis in the preterm infant. However, as breastfeeding is not possible for the very premature infant, human milk needs to be introduced in the neonatal intensive care unit through alternative means, resulting in significant handling and manipulation of maternal milk. This presents risks in quality control and provision of optimal nutrition delivery. Therefore, a comprehensive approach to standardizing preterm infant nutrition is essential to optimize the collection, storage, fortification and delivery of human milk to preterm neonates. In this paper we discuss the challenges presented by supporting human milk nutrition, and the rationale for the development of the Supporting Premature Infant Nutrition (SPIN) program at our institution. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction 1.1. Gut immaturity The developing gastrointestinal (GI) tract, like other organs, structurally forms early in gestation but the functional facets of this organ take longer to develop. In particular, the digestive, absorptive and motor capacities are still maturing [1]. Certain aspects of digestion, such as lactase activity, have been shown to improve with enteral feeding. However, other functions such as migratory motor complexes follow a more fixed developmental timeline, not maturing until closer to term corrected age [2,3]. It is no surprise that the preterm gut is particularly sensitive to injury due to the immaturity of all aspects of its function in addition to a list of other vulnerabilities that the preterm infant faces (Table 1). The gut is unprepared for enteral nutrition due to an immature immune system, underdeveloped physical mucosal barrier (leaky tight junctions, reduced mucin layer), poor acid production, abnormal bacterial colonization and poor motility. Combined, these factors make the preterm bowel susceptible to injury from systemic ischemia, acidosis or infection. 1.2. Feeding the preterm infants In the past, concern for the immaturity of the GI tract of the preterm infant resulted in cautious feeding regimens that delayed the initiation ⁎ Corresponding author. E-mail address: [email protected] (J.H. Kim).
of enteral feeds for up to several weeks. Coupled with the fact that HM was not always readily available through the use of pumping or access to pasteurized donor milk, the use of infant formula (IF) was frequently initiated first. Subsequently, earlier enteral feedings have been found to be trophic and protective to the gut. While designed to optimize nutrient delivery for growth, IF may be introducing foreign substrates and less immunologic complexity than HM into the premature gut. Human milk (HM) is now considered the ideal feeding choice for the preterm infant. In addition, standardized feeding protocols have been associated with reduced rates of necrotizing enterocolitis (NEC) [4]. 1.3. Infant formula as a nutritional replacement Infant formula is a milk substitute made up of a sophisticated mixture of reconstituted animal milk proteins and sugars along with plant based oils and numerous nutritional additives to approximate the nutritional components of HM [2]. IF has very little in the way of bioactivity. This is by design, as commercial manufacturers of IF do not have the capacity or financial incentives to reconstitute IF with numerous bioactive compounds. Further, there are no cellular components in IF aside from the addition of probiotics in term formula. Therefore IF is primarily seen as a substitute for HM nutrients, not as a substitute for the immunologically active components of HM. 1.4. What is in human milk? A key paradigm shift takes place with the full recognition of the biologic activity of HM making it much more than an ideal source of
0378-3782/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002
Please cite this article as: Kim JH, et al, Challenges in the practice of human milk nutrition in the neonatal intensive care unit, Early Hum Dev (2013), http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002
2
J.H. Kim et al. / Early Human Development xxx (2013) xxx–xxx
Table 1 Vulnerabilities of the preterm infant. • • • • • • • •
Increased risk of necrotizing enterocolitis Poor neurocognitive outcomes Increased risk for infection Decreased immunoglobulins Increased intestinal permeability Poor intestinal motility Abnormal gut colonization Delayed gastric emptying
All these problems are improved by feeding human milk.
nutrients for the preterm infant. The properties of HM are incredibly diverse and include a long list of biologically active factors and cellular functions.
1.5. Nutritional components of HM HM is a biologically active liquid tissue produced by lactating mothers after delivery. Like another liquid tissue, blood, HM contains immune cells, hormones, enzymes, cytokines and other immune modulators as well as nutritional components unique to humans. The macronutrient composition is a rich combination of proteins, carbohydrates, and lipids. The protein concentration differs from infant formulas by having species-specific proteins as well as a different profile of caseins and whey proteins. The carbohydrate content is primarily lactose. But HM uniquely includes an abundance of oligosaccharides; short chain sugars that are genetically predetermined and act as prebiotics with gut epithelial and immune modulating properties [5]. Finally human milk lipid composition also differs greatly from infant formula lipids. Human fat globules are much larger than those of bovine milk and their structure is uniquely constructed with a glycolipid and glycoprotein enriched lipid bilayer [6].
1.8. Benefits of human milk for the preterm infant There is a large body of clinical data to support that human milk intake reduces the incidence and severity of NEC. Sullivan and colleagues demonstrated that an exclusively human diet dramatically reduced the incidence of overall NEC and surgical NEC [11]. Re-analysis of the same dataset also showed a reduction of days of parenteral nutrition when the total cumulative days were added together throughout the hospital stay [12]. In review of the nutrition data from the glutamine trial, a multicenter cohort of infants from the NICHD Neonatal Research Network, the fractional human milk intake in preterm infants was directly correlated to the survival free NEC risk [13]. An older study by Lucas and Cole in 1990 demonstrated a strong relationship between expressed breast milk intake and protection against NEC [14]. Other demonstrated benefits of HM on preterm infants include quicker attainment of full feeds, shorter NICU stay, less hospital readmission, and cognitive improvement (higher Bayley 2 development scores and intelligence quotient) [15,16]. The most recent studies include several human donor milk (DM) trials. There remains some controversy as to the effects of DM on NEC. A Cochrane review in addition to systematic reviews has been inconclusive in defining a clear benefit of exclusive DM and NEC reduction [17,18]. Future studies of larger size are required to determine the impact of DM independent of MM. 1.9. Economic impact of NEC There is now sufficient evidence to make a strong argument economically that all extremely premature infants receive exclusively human milk as their base nutrition. These studies have demonstrated that with current data, and an average NEC rate in the NICU, significant cost savings are appreciated by treating all infants less than 1250 g birthweight with human milk products. The primary reason for this is the dramatic cost that a single case of medical NEC (~USD 70 K) or surgical NEC (~USD 200 K) incurs over the hospital stay [19,20].
1.6. Non-nutritional components of human milk
1.10. Overall perspective on NEC
The number of non-nutritional components of HM far outnumbers the nutritional ones. These factors include antimicrobial factors, cytokines, anti-inflammatory factor, hormones, growth factors, digestive enzymes, and transporters [7]. HM also contains numerous cell types such as lymphocytes, macrophages, neutrophils, natural killer cells, as well as probiotic bacteria. HM contains several different lipases that are activated in the small bowel where it can assist the digestion of the milk itself. Human milk bioactivity is unique to humans too. Many of the bioactive factors help advance gastrointestinal maturity along several aspects of the gut, not just the mucosal epithelium but also the gut nervous and immune systems [8].
In the past three decades, we have seen a changing NEC demographic [21]. In the past, much more mature infants were getting NEC. Increasing survival in the smallest preterm infant category, those less than 29 weeks gestation, has continued to keep NEC incidence stable (http://www.vtoxford.org). There are now several units that are now demonstrating persistent low to zero NEC rates by use of conservative feeding protocols and exclusive use of human milk [22]. It is therefore altogether possible for us to speculate that NEC can be reduced to very low rates with the introduction of clear consistent practices. 2. Issues in providing human milk to preterm infants 2.1. Milk handling
1.7. Benefits of human milk for the term infant Preterm infants benefit from the same long list of benefits of HM for the term infant that include a multitude of health benefits including short and long-term benefits over infant formula (IF) feeding [9]. Short-term benefits of HM over IF include a reduction in numerous morbidity outcomes in childhood including otitis media, pneumonia, diarrhea, bacteremia, and urinary tract infection [9,10]. Interestingly HM is responsible for a reduction in infant mortality around the world with a reduction in sudden infant death syndrome in developed countries and infection in developing countries. Long-term benefits of HM over IF include improved cognitive development, reductions in allergy/ asthma, celiac disease, metabolic syndrome and short bowel syndrome. Maternal benefits of lactation include a reduction in ovarian and breast cancer, as well as reduction in metabolic and cardiovascular morbidities.
The increasing use of HM along with variable fortification strategies has presented new problems of quality control. HM comes into the hospital in a multitude of ways and much of this is poorly regulated (Fig. 1). Mothers pump at home or in hospital, and bring in milk either fresh or frozen, with little quality control in regards to rules of cleaning, storage, or transport. 2.2. Quality of HM Due to the complex and organic nature of HM the risk of deteriorating quality of HM is evident from the moment HM is expressed. These risks include damage by oxidation, photo-degradation and bacterial contamination. Also, excessive handling and transfer increases the risk of nutrient loss with each material surface the milk is in contact with.
Please cite this article as: Kim JH, et al, Challenges in the practice of human milk nutrition in the neonatal intensive care unit, Early Hum Dev (2013), http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002
J.H. Kim et al. / Early Human Development xxx (2013) xxx–xxx
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2.5. Warming HM Bringing frozen or refrigerated milk to feeding temperature (either room temperature or body temperature) is not properly standardized in NICU's across North America. Several commercial options are now available that offer controlled thawing and/or warming of HM. These are preferable as unmonitored heating may reduce bioactive factors in human milk. Microwaving, in particular, should not be avoided due to “hotspots” that can be generated. 2.6. Measuring nutrient content in HM There are now several options by which the nutrient content of HM can be measured. These include creamatocrit, mid-infrared and near infrared spectrophotometry [23,27,28]. Alternative strategies without the use of milk analysis include adjustable fortification approaches using the blood urea nitrogen to determine appropriate protein intake [29]. 2.7. Role of a milk lab and milk technician
Fig. 1. The human milk journey.
Further risks can occur with repeated handling, freezing and heating. Freezing destroys most immune cells such as neutrophils or macrophages but does not damage bacteria significantly. 2.3. Properties of HM Human milk nutrient content has been shown to be highly variable between individual mothers, time of day, degree of breast emptying, and phase of lactation. There are no good determinants of this variability with well nourished mothers [23]. For example, in the first month of lactation, there is a loss of approximately 25% in total protein in the first month with a more gradual decline thereafter even out to six months of lactation [24]. This is relevant to donor milk banking as the predominant milk donated comes from mothers of term infants who are several months of age. This naturally results in a lower mean protein content of donor milk. 2.4. Collection, storage and transport of HM Frequent pumping into individual containers generates a significant amount of work for mothers. The pumped milk needs to be labeled and dated, equipment needs to be cleaned, and mothers pump 6 to 8 times each day. There are benefits of pooling HM that include maternal satisfaction, easier tracking of daily lactation production volume, and same or reduced bacterial counts [25]. Ideally HM collection containers should be standardized to minimize contamination risks, improve nutrient content, and decrease maternal workload. Stored HM is generally kept in a frozen state at −20 °C. Recent data would support, however, the use of refrigerated (+4 °C) milk for at least 96 h [26]. This would eliminate any untoward effects that might occur with prolonged freezing. Keeping HM in a refrigerated state for less than four days slightly decreased pH, reduced WBC, reduced protein and gram positive bacterial counts. Increases were seen in free fatty acids from active lipolysis. No changes in osmolality, secretory IgA, fat, gram negative bacteria, and lactoferrin were noted. Thus cold human milk retains optimal nutrient profile and a safe content for 96 h after expression. Optimal freezer organization includes individual covered bins, proper freezer alarms and ready access of freezers to clinical care. Transporting of HM from home should be standardized by maintaining cooled or frozen milk in an insulated container packed with ice or freezer packs.
With increasing complexity in human milk feeding options and greater individualization of nutrient delivery; centralizing HM processing and fortification processes may be of benefit. A dedicated space with all available storage and supplies may increase the workflow productivity of a large unit while reducing the chance for milk contamination. Some NICUs employ milk technicians who are responsible for collecting the daily milk order, using standard recipes to mix daily feedings, warming milk through consistent practice, drawing up each feeding into syringes for enteral tube feeding or large bottles with oral feeding. We found that there were many other benefits of a milk technician including reduction in nursing workload, consistent preparation practices, reduced number of staff to train, and overall better quality control of HM. Newer tasks may also include routine milk analysis to further optimize the nutritional quality of the final milk mixture. 2.8. Feeding of HM The use of HM through enteral feeding systems has been shown to be a source of significant loss of nutrients [30,31]. This is particularly relevant with syringe loaded feeding systems where due to the separation and rise of the fat globules, a level or inverted position of the syringe is less favorable than an upright position (spout up). Since milk fat adheres to containers it is important to reduce transfers from containers, minimize continuous syringe pump feedings, and keep syringes facing upwards during feedings. 2.9. Description of the SPIN program In 2007, in response to the above mentioned challenges in the practice of human milk nutrition and a strong desire to standardize care in this area, at UC, San Diego, Medical Center (UCSDMC), we developed the SPIN (Supporting Premature Infant Nutrition) program, a multifaceted, multidisciplinary program to improve neonatal nutrition practices and increase human milk intact in preterm infants (http://spinprogram. ucsd.edu). It was prefaced in 2006 with becoming the first academic Baby Friendly Hospital Initiative (BFHI) in California. BFHI USA has demonstrated that rates of in-hospital rates of breastfeeding initiation rates in healthy term newborns dramatically go up with the implementation of program strategies. Given the success of the BFHI for healthy term infants, we wished to extend the same benefits of human milk delivery to more vulnerable preterm infants in the NICU. The groundwork for the BFHI was first developed at UCSDMC (http://www.babyfriendlyusa. org). The major structural innovation of the SPIN program was the collaboration of the nutrition and lactation stakeholders in the hospital. This brought key stakeholders to develop common goals and objectives for
Please cite this article as: Kim JH, et al, Challenges in the practice of human milk nutrition in the neonatal intensive care unit, Early Hum Dev (2013), http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002
4
J.H. Kim et al. / Early Human Development xxx (2013) xxx–xxx
Table 2 SPIN Ten Steps. 1. Have a NICU human milk nutrition policy 2. Educate all mother/baby staff in SPIN Ten Steps 3. Educate NICU families about optimal premature infant nutrition 4. Prevent extrauterine growth restriction 5. Standardize enteral feeding process 6. Target 100% human milk nutrition 7. Maximize mothers' milk production 8. Optimize milk quality and safety standards 9. Encourage skin-to-skin care and breastfeeding 10. Provide a nutrition and lactation discharge plan from NICU
the best interest in growing healthier preterm infants. The overarching mission statement for the SPIN program was to create a center of excellence in neonatal nutrition focused on the provision, analysis, and research of human milk to improve nutritional and long-term health outcomes of premature babies. The other important facets of the program include following the SPIN Ten Steps (Table 2) and setting up outpatient follow-up (premature infant nutrition community (PINC) clinic), community outreach to other cities through lecture series, and human milk nutrition research. We have learned several lessons in creating the SPIN program. Key aspects of our program that were foundational in this comprehensive program were to form a multidisciplinary group, administrative support, involvement of all stakeholders, performance of a self-assessment, setting specific goals and timelines, regular team meetings, providing staff updates, and collection of key outcome data. Through this we stimulated behavior and attitude change by all health care professionals, and set a new standard for HM as the preferred feeding in our unit. 3. Conclusion The myriad of potent properties in HM offers the best chance for an optimal outcome for the extremely premature infant. Increasing HM intake by preterm infants presents a new set of issues that can be best addressed by establishing a formal program of standardization of clinical care around HM nutrition. Conflict of interest Jae Kim: Medela Speaker, Research Grant Abbott Nutrition Speaker, Research Grant, Advisory Board Nestle Nutrition Speaker, Advisory Board Mead Johnson Speaker Nutricia Speaker Acacia Advisory Board, Consultant Pedia Solutions Advisory Board, Stockholder Lisa Stellwagen: Medela Speaker, Research Grant Tina Chan and Yvonne Vaucher have no conflict of interest to report. Acknowledgments We thank all the staff at UC San Diego Medical Center, and the SPIN mothers who participated in providing crucial feedback during program development. References [1] Commare CE, Tappenden KA. Development of the infant intestine: implications for nutrition support. Nutr Clin Pract 2007;22:159–73.
[2] Klein CJ. Nutrient requirements for preterm infant formulas. J Nutr 2002;132: 1395S–577S. [3] Shulman RJ, Wong WW, Smith EO. Influence of changes in lactase activity and small-intestinal mucosal growth on lactose digestion and absorption in preterm infants. Am J Clin Nutr 2005;81:472–9. [4] Bombell S, McGuire W. Early trophic feeding for very low birth weight infants. Cochrane Database Syst Rev 2009:CD000504. [5] Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology 2012;22:1147–62. [6] Michalski MC, Briard V, Michel F, Tasson F, Poulain P. Size distribution of fat globules in human colostrum, breast milk, and infant formula. J Dairy Sci 2005;88:1927–40. [7] Kim JH, Froh EB. What nurses need to know regarding nutritional and immunobiological properties of human milk. J Obstet Gynecol Neonatal Nurs 2011;41(1): 122–37. [8] Goldman AS. The immune system in human milk and the developing infant. Breastfeed Med 2007;2:195–204. [9] Breastfeeding and the use of human milk. Pediatrics 2012;129:e827–41. [10] Andorsky DJ, Lund DP, Lillehei CW, Jaksic T, Dicanzio J, Richardson DS, et al. Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes. J Pediatr 2001;139:27–33. [11] Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U, 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;156:562–7. [12] Ghandehari H, Lee ML, Rechtman DJ, Group HMS. An exclusive human milk-based diet in extremely premature infants reduces the probability of remaining on total parenteral nutrition: a reanalysis of the data. BMC Res Notes 2012;5:188. [13] Meinzen-Derr J, Poindexter B, Wrage L, Morrow AL, Stoll B, Donovan EF. Role of human milk in extremely low birth weight infants' risk of necrotizing enterocolitis or death. J Perinatol 2009;29:57–62. [14] Lucas A, Cole TJ. Breast milk and neonatal necrotising enterocolitis. Lancet 1990;336: 1519–23. [15] Vohr BR, Wright LL, Dusick AM, Mele L, Verter J, Steichen JJ, et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993–1994. Pediatrics 2000;105:1216–26. [16] Isaacs EB, Fischl BR, Quinn BT, Chong WK, Gadian DG, Lucas A. Impact of breast milk on IQ, brain size and white matter development. Pediatr Res 2009;67(4):357–62. [17] 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:CD002971. [18] 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:F169–75. [19] Ganapathy V, Hay JW, Kim JH. Costs of necrotizing enterocolitis and costeffectiveness of exclusively human milk-based products in feeding extremely premature infants. Breastfeed Med 2012;7:29–37. [20] Bisquera JA, Cooper TR, Berseth CL. Impact of necrotizing enterocolitis on length of stay and hospital charges in very low birth weight infants. Pediatrics 2002;109:423–8. [21] Sharma R, Hudak ML. A clinical perspective of necrotizing enterocolitis: past, present, and future. Clin Perinatol 2013;40:27–51. [22] Pietz J, Achanti B, Lilien L, Stepka EC, Mehta SK. Prevention of necrotizing enterocolitis in preterm infants: a 20-year experience. Pediatrics 2007;119:e164–70. [23] Sauer CW, Kim JH. Human milk macronutrient analysis using point-of-care near-infrared spectrophotometry. J Perinatol 2011;31:339–43. [24] 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: 1176–81. [25] Stellwagen LM, Vaucher YE, Chan CS, Montminy TD, Kim JH. Pooling expressed breastmilk to provide a consistent feeding composition for premature infants. Breastfeed Med 2012;8(2):205–9. [26] Slutzah M, Codipilly CN, Potak D, Clark RM, Schanler RJ. Refrigerator storage of expressed human milk in the neonatal intensive care unit. J Pediatr 2010;156: 26–8. [27] Wang CD, Chu PS, Mellen BG, Shenai JP. Creamatocrit and the nutrient composition of human milk. J Perinatol 1999;19:343–6. [28] Casadio YS, Williams TM, Lai CT, Olsson SE, Hepworth AR, Hartmann PE. Evaluation of a mid-infrared analyzer for the determination of the macronutrient composition of human milk. J Hum Lact 2010;26:376–83. [29] Arslanoglu S, Moro GE, Ziegler EE. Adjustable fortification of human milk fed to preterm infants: does it make a difference? J Perinatol 2006;26:614–21. [30] Tacken KJ, Vogelsang A, van Lingen RA, Slootstra J, Dikkeschei BD, van ZoerenGrobben D. Loss of triglycerides and carotenoids in human milk after processing. Arch Dis Child Fetal Neonatal Ed 2009;94:F447–50. [31] Rogers SP, Hicks PD, Hamzo M, Veit LE, Abrams SA. Continuous feedings of fortified human milk lead to nutrient losses of fat, calcium and phosphorous. Nutrients 2010;2:230–40.
Please cite this article as: Kim JH, et al, Challenges in the practice of human milk nutrition in the neonatal intensive care unit, Early Hum Dev (2013), http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002
Contents lists available at ScienceDirect
Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
Challenges in the practice of human milk nutrition in the neonatal intensive care unit Jae H. Kim ⁎, Christina S. Chan, Yvonne E. Vaucher, Lisa M. Stellwagen University of California, San Diego, 200 West Arbor Dr. MPF 1140, San Diego, CA 92103-8774, USA
a r t i c l e
i n f o
Available online xxxx
a b s t r a c t The use of human milk for preterm infants has increased over the past decade reflecting an improved awareness of the benefits of human milk. Inherent in this paradigm shift is the recognition that human milk is a living tissue; full of immune cells, probiotics and hundreds of compounds that confer bioactivity and immune protective properties. Together these factors deliver a powerful effect in reducing clinical morbidities such as necrotizing enterocolitis and sepsis in the preterm infant. However, as breastfeeding is not possible for the very premature infant, human milk needs to be introduced in the neonatal intensive care unit through alternative means, resulting in significant handling and manipulation of maternal milk. This presents risks in quality control and provision of optimal nutrition delivery. Therefore, a comprehensive approach to standardizing preterm infant nutrition is essential to optimize the collection, storage, fortification and delivery of human milk to preterm neonates. In this paper we discuss the challenges presented by supporting human milk nutrition, and the rationale for the development of the Supporting Premature Infant Nutrition (SPIN) program at our institution. © 2013 Elsevier Ireland Ltd. All rights reserved.
1. Introduction 1.1. Gut immaturity The developing gastrointestinal (GI) tract, like other organs, structurally forms early in gestation but the functional facets of this organ take longer to develop. In particular, the digestive, absorptive and motor capacities are still maturing [1]. Certain aspects of digestion, such as lactase activity, have been shown to improve with enteral feeding. However, other functions such as migratory motor complexes follow a more fixed developmental timeline, not maturing until closer to term corrected age [2,3]. It is no surprise that the preterm gut is particularly sensitive to injury due to the immaturity of all aspects of its function in addition to a list of other vulnerabilities that the preterm infant faces (Table 1). The gut is unprepared for enteral nutrition due to an immature immune system, underdeveloped physical mucosal barrier (leaky tight junctions, reduced mucin layer), poor acid production, abnormal bacterial colonization and poor motility. Combined, these factors make the preterm bowel susceptible to injury from systemic ischemia, acidosis or infection. 1.2. Feeding the preterm infants In the past, concern for the immaturity of the GI tract of the preterm infant resulted in cautious feeding regimens that delayed the initiation ⁎ Corresponding author. E-mail address: [email protected] (J.H. Kim).
of enteral feeds for up to several weeks. Coupled with the fact that HM was not always readily available through the use of pumping or access to pasteurized donor milk, the use of infant formula (IF) was frequently initiated first. Subsequently, earlier enteral feedings have been found to be trophic and protective to the gut. While designed to optimize nutrient delivery for growth, IF may be introducing foreign substrates and less immunologic complexity than HM into the premature gut. Human milk (HM) is now considered the ideal feeding choice for the preterm infant. In addition, standardized feeding protocols have been associated with reduced rates of necrotizing enterocolitis (NEC) [4]. 1.3. Infant formula as a nutritional replacement Infant formula is a milk substitute made up of a sophisticated mixture of reconstituted animal milk proteins and sugars along with plant based oils and numerous nutritional additives to approximate the nutritional components of HM [2]. IF has very little in the way of bioactivity. This is by design, as commercial manufacturers of IF do not have the capacity or financial incentives to reconstitute IF with numerous bioactive compounds. Further, there are no cellular components in IF aside from the addition of probiotics in term formula. Therefore IF is primarily seen as a substitute for HM nutrients, not as a substitute for the immunologically active components of HM. 1.4. What is in human milk? A key paradigm shift takes place with the full recognition of the biologic activity of HM making it much more than an ideal source of
0378-3782/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002
Please cite this article as: Kim JH, et al, Challenges in the practice of human milk nutrition in the neonatal intensive care unit, Early Hum Dev (2013), http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002
2
J.H. Kim et al. / Early Human Development xxx (2013) xxx–xxx
Table 1 Vulnerabilities of the preterm infant. • • • • • • • •
Increased risk of necrotizing enterocolitis Poor neurocognitive outcomes Increased risk for infection Decreased immunoglobulins Increased intestinal permeability Poor intestinal motility Abnormal gut colonization Delayed gastric emptying
All these problems are improved by feeding human milk.
nutrients for the preterm infant. The properties of HM are incredibly diverse and include a long list of biologically active factors and cellular functions.
1.5. Nutritional components of HM HM is a biologically active liquid tissue produced by lactating mothers after delivery. Like another liquid tissue, blood, HM contains immune cells, hormones, enzymes, cytokines and other immune modulators as well as nutritional components unique to humans. The macronutrient composition is a rich combination of proteins, carbohydrates, and lipids. The protein concentration differs from infant formulas by having species-specific proteins as well as a different profile of caseins and whey proteins. The carbohydrate content is primarily lactose. But HM uniquely includes an abundance of oligosaccharides; short chain sugars that are genetically predetermined and act as prebiotics with gut epithelial and immune modulating properties [5]. Finally human milk lipid composition also differs greatly from infant formula lipids. Human fat globules are much larger than those of bovine milk and their structure is uniquely constructed with a glycolipid and glycoprotein enriched lipid bilayer [6].
1.8. Benefits of human milk for the preterm infant There is a large body of clinical data to support that human milk intake reduces the incidence and severity of NEC. Sullivan and colleagues demonstrated that an exclusively human diet dramatically reduced the incidence of overall NEC and surgical NEC [11]. Re-analysis of the same dataset also showed a reduction of days of parenteral nutrition when the total cumulative days were added together throughout the hospital stay [12]. In review of the nutrition data from the glutamine trial, a multicenter cohort of infants from the NICHD Neonatal Research Network, the fractional human milk intake in preterm infants was directly correlated to the survival free NEC risk [13]. An older study by Lucas and Cole in 1990 demonstrated a strong relationship between expressed breast milk intake and protection against NEC [14]. Other demonstrated benefits of HM on preterm infants include quicker attainment of full feeds, shorter NICU stay, less hospital readmission, and cognitive improvement (higher Bayley 2 development scores and intelligence quotient) [15,16]. The most recent studies include several human donor milk (DM) trials. There remains some controversy as to the effects of DM on NEC. A Cochrane review in addition to systematic reviews has been inconclusive in defining a clear benefit of exclusive DM and NEC reduction [17,18]. Future studies of larger size are required to determine the impact of DM independent of MM. 1.9. Economic impact of NEC There is now sufficient evidence to make a strong argument economically that all extremely premature infants receive exclusively human milk as their base nutrition. These studies have demonstrated that with current data, and an average NEC rate in the NICU, significant cost savings are appreciated by treating all infants less than 1250 g birthweight with human milk products. The primary reason for this is the dramatic cost that a single case of medical NEC (~USD 70 K) or surgical NEC (~USD 200 K) incurs over the hospital stay [19,20].
1.6. Non-nutritional components of human milk
1.10. Overall perspective on NEC
The number of non-nutritional components of HM far outnumbers the nutritional ones. These factors include antimicrobial factors, cytokines, anti-inflammatory factor, hormones, growth factors, digestive enzymes, and transporters [7]. HM also contains numerous cell types such as lymphocytes, macrophages, neutrophils, natural killer cells, as well as probiotic bacteria. HM contains several different lipases that are activated in the small bowel where it can assist the digestion of the milk itself. Human milk bioactivity is unique to humans too. Many of the bioactive factors help advance gastrointestinal maturity along several aspects of the gut, not just the mucosal epithelium but also the gut nervous and immune systems [8].
In the past three decades, we have seen a changing NEC demographic [21]. In the past, much more mature infants were getting NEC. Increasing survival in the smallest preterm infant category, those less than 29 weeks gestation, has continued to keep NEC incidence stable (http://www.vtoxford.org). There are now several units that are now demonstrating persistent low to zero NEC rates by use of conservative feeding protocols and exclusive use of human milk [22]. It is therefore altogether possible for us to speculate that NEC can be reduced to very low rates with the introduction of clear consistent practices. 2. Issues in providing human milk to preterm infants 2.1. Milk handling
1.7. Benefits of human milk for the term infant Preterm infants benefit from the same long list of benefits of HM for the term infant that include a multitude of health benefits including short and long-term benefits over infant formula (IF) feeding [9]. Short-term benefits of HM over IF include a reduction in numerous morbidity outcomes in childhood including otitis media, pneumonia, diarrhea, bacteremia, and urinary tract infection [9,10]. Interestingly HM is responsible for a reduction in infant mortality around the world with a reduction in sudden infant death syndrome in developed countries and infection in developing countries. Long-term benefits of HM over IF include improved cognitive development, reductions in allergy/ asthma, celiac disease, metabolic syndrome and short bowel syndrome. Maternal benefits of lactation include a reduction in ovarian and breast cancer, as well as reduction in metabolic and cardiovascular morbidities.
The increasing use of HM along with variable fortification strategies has presented new problems of quality control. HM comes into the hospital in a multitude of ways and much of this is poorly regulated (Fig. 1). Mothers pump at home or in hospital, and bring in milk either fresh or frozen, with little quality control in regards to rules of cleaning, storage, or transport. 2.2. Quality of HM Due to the complex and organic nature of HM the risk of deteriorating quality of HM is evident from the moment HM is expressed. These risks include damage by oxidation, photo-degradation and bacterial contamination. Also, excessive handling and transfer increases the risk of nutrient loss with each material surface the milk is in contact with.
Please cite this article as: Kim JH, et al, Challenges in the practice of human milk nutrition in the neonatal intensive care unit, Early Hum Dev (2013), http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002
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2.5. Warming HM Bringing frozen or refrigerated milk to feeding temperature (either room temperature or body temperature) is not properly standardized in NICU's across North America. Several commercial options are now available that offer controlled thawing and/or warming of HM. These are preferable as unmonitored heating may reduce bioactive factors in human milk. Microwaving, in particular, should not be avoided due to “hotspots” that can be generated. 2.6. Measuring nutrient content in HM There are now several options by which the nutrient content of HM can be measured. These include creamatocrit, mid-infrared and near infrared spectrophotometry [23,27,28]. Alternative strategies without the use of milk analysis include adjustable fortification approaches using the blood urea nitrogen to determine appropriate protein intake [29]. 2.7. Role of a milk lab and milk technician
Fig. 1. The human milk journey.
Further risks can occur with repeated handling, freezing and heating. Freezing destroys most immune cells such as neutrophils or macrophages but does not damage bacteria significantly. 2.3. Properties of HM Human milk nutrient content has been shown to be highly variable between individual mothers, time of day, degree of breast emptying, and phase of lactation. There are no good determinants of this variability with well nourished mothers [23]. For example, in the first month of lactation, there is a loss of approximately 25% in total protein in the first month with a more gradual decline thereafter even out to six months of lactation [24]. This is relevant to donor milk banking as the predominant milk donated comes from mothers of term infants who are several months of age. This naturally results in a lower mean protein content of donor milk. 2.4. Collection, storage and transport of HM Frequent pumping into individual containers generates a significant amount of work for mothers. The pumped milk needs to be labeled and dated, equipment needs to be cleaned, and mothers pump 6 to 8 times each day. There are benefits of pooling HM that include maternal satisfaction, easier tracking of daily lactation production volume, and same or reduced bacterial counts [25]. Ideally HM collection containers should be standardized to minimize contamination risks, improve nutrient content, and decrease maternal workload. Stored HM is generally kept in a frozen state at −20 °C. Recent data would support, however, the use of refrigerated (+4 °C) milk for at least 96 h [26]. This would eliminate any untoward effects that might occur with prolonged freezing. Keeping HM in a refrigerated state for less than four days slightly decreased pH, reduced WBC, reduced protein and gram positive bacterial counts. Increases were seen in free fatty acids from active lipolysis. No changes in osmolality, secretory IgA, fat, gram negative bacteria, and lactoferrin were noted. Thus cold human milk retains optimal nutrient profile and a safe content for 96 h after expression. Optimal freezer organization includes individual covered bins, proper freezer alarms and ready access of freezers to clinical care. Transporting of HM from home should be standardized by maintaining cooled or frozen milk in an insulated container packed with ice or freezer packs.
With increasing complexity in human milk feeding options and greater individualization of nutrient delivery; centralizing HM processing and fortification processes may be of benefit. A dedicated space with all available storage and supplies may increase the workflow productivity of a large unit while reducing the chance for milk contamination. Some NICUs employ milk technicians who are responsible for collecting the daily milk order, using standard recipes to mix daily feedings, warming milk through consistent practice, drawing up each feeding into syringes for enteral tube feeding or large bottles with oral feeding. We found that there were many other benefits of a milk technician including reduction in nursing workload, consistent preparation practices, reduced number of staff to train, and overall better quality control of HM. Newer tasks may also include routine milk analysis to further optimize the nutritional quality of the final milk mixture. 2.8. Feeding of HM The use of HM through enteral feeding systems has been shown to be a source of significant loss of nutrients [30,31]. This is particularly relevant with syringe loaded feeding systems where due to the separation and rise of the fat globules, a level or inverted position of the syringe is less favorable than an upright position (spout up). Since milk fat adheres to containers it is important to reduce transfers from containers, minimize continuous syringe pump feedings, and keep syringes facing upwards during feedings. 2.9. Description of the SPIN program In 2007, in response to the above mentioned challenges in the practice of human milk nutrition and a strong desire to standardize care in this area, at UC, San Diego, Medical Center (UCSDMC), we developed the SPIN (Supporting Premature Infant Nutrition) program, a multifaceted, multidisciplinary program to improve neonatal nutrition practices and increase human milk intact in preterm infants (http://spinprogram. ucsd.edu). It was prefaced in 2006 with becoming the first academic Baby Friendly Hospital Initiative (BFHI) in California. BFHI USA has demonstrated that rates of in-hospital rates of breastfeeding initiation rates in healthy term newborns dramatically go up with the implementation of program strategies. Given the success of the BFHI for healthy term infants, we wished to extend the same benefits of human milk delivery to more vulnerable preterm infants in the NICU. The groundwork for the BFHI was first developed at UCSDMC (http://www.babyfriendlyusa. org). The major structural innovation of the SPIN program was the collaboration of the nutrition and lactation stakeholders in the hospital. This brought key stakeholders to develop common goals and objectives for
Please cite this article as: Kim JH, et al, Challenges in the practice of human milk nutrition in the neonatal intensive care unit, Early Hum Dev (2013), http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002
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Table 2 SPIN Ten Steps. 1. Have a NICU human milk nutrition policy 2. Educate all mother/baby staff in SPIN Ten Steps 3. Educate NICU families about optimal premature infant nutrition 4. Prevent extrauterine growth restriction 5. Standardize enteral feeding process 6. Target 100% human milk nutrition 7. Maximize mothers' milk production 8. Optimize milk quality and safety standards 9. Encourage skin-to-skin care and breastfeeding 10. Provide a nutrition and lactation discharge plan from NICU
the best interest in growing healthier preterm infants. The overarching mission statement for the SPIN program was to create a center of excellence in neonatal nutrition focused on the provision, analysis, and research of human milk to improve nutritional and long-term health outcomes of premature babies. The other important facets of the program include following the SPIN Ten Steps (Table 2) and setting up outpatient follow-up (premature infant nutrition community (PINC) clinic), community outreach to other cities through lecture series, and human milk nutrition research. We have learned several lessons in creating the SPIN program. Key aspects of our program that were foundational in this comprehensive program were to form a multidisciplinary group, administrative support, involvement of all stakeholders, performance of a self-assessment, setting specific goals and timelines, regular team meetings, providing staff updates, and collection of key outcome data. Through this we stimulated behavior and attitude change by all health care professionals, and set a new standard for HM as the preferred feeding in our unit. 3. Conclusion The myriad of potent properties in HM offers the best chance for an optimal outcome for the extremely premature infant. Increasing HM intake by preterm infants presents a new set of issues that can be best addressed by establishing a formal program of standardization of clinical care around HM nutrition. Conflict of interest Jae Kim: Medela Speaker, Research Grant Abbott Nutrition Speaker, Research Grant, Advisory Board Nestle Nutrition Speaker, Advisory Board Mead Johnson Speaker Nutricia Speaker Acacia Advisory Board, Consultant Pedia Solutions Advisory Board, Stockholder Lisa Stellwagen: Medela Speaker, Research Grant Tina Chan and Yvonne Vaucher have no conflict of interest to report. Acknowledgments We thank all the staff at UC San Diego Medical Center, and the SPIN mothers who participated in providing crucial feedback during program development. References [1] Commare CE, Tappenden KA. Development of the infant intestine: implications for nutrition support. Nutr Clin Pract 2007;22:159–73.
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Please cite this article as: Kim JH, et al, Challenges in the practice of human milk nutrition in the neonatal intensive care unit, Early Hum Dev (2013), http://dx.doi.org/10.1016/j.earlhumdev.2013.08.002