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16 Human Milk in the Neonatal Intensive Care Unit

Published onJul 01, 2018
16 Human Milk in the Neonatal Intensive Care Unit

16 Human Milk in the Neonatal Intensive Care Unit

Paula P. Meier, Prof, PhD, RN, FAAN; Beverly Rossman, PhD, RN; Aloka L. Patel, MD; Tricia J. Johnson, PhD; Janet L. Engstrom, PhD, APN, CNM, WHNP-BC, CNE; Rebecca A. Hoban, MD, MPH; Kousiki Patra, MD; Harold R. Bigger, MD

Expected Key Learning Outcomes

  • Successful feeding option for premature infants in a neonatal intensive care unit

  • Why human milk is so vital to preterm and vulnerable infants

  • How human milk provides protection from multiple short- and long-term morbidities

  • Approaches to enable preterm mothers to provide enough milk for their infants

16.1 Introduction

Human milk (HM, milk from the infant’s own mother) feeding of premature infants during hospitalisation in a neonatal intensive care unit (NICU) reduces the risk of multiple short and longterm complications, including necrotising enterocolitis (NEC), late onset sepsis (sepsis), chronic lung disease (CLD), retinopathy of prematurity (ROP), rehospitalisation after NICU discharge, and neurodevelopmental problems in infancy and childhood [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. The benefit is dose related, with larger amounts (doses) of HM translating into greater risk reductions for these morbidities during specific critical development periods that occur while hospitalised [1][5], [8][10],[12], [13], [14], [15], [16], [17], [18], [19], [20]. Furthermore, by reducing the risk of these morbidities, HM feedings represent a safe and effective mechanism to lower health care costs that are associated with them and their sequelae [4], [8], [15], [21], [22]. Donor HM does not provide this same protection [6], [23] and commercially-available formulas increase the risk of these morbidities in premature infants [8], [24], [25], [26]. Thus, interventions that target the initiation and maintenance of maternal lactation and the exclusive use of HM are priorities worldwide for this vulnerable population [18], [19], [27].

This chapter reviews the health outcomes and costs of HM feedings for premature infants. It describes the mechanisms by which HM functions to protect immature organs and physiological pathways from NICU stressors of inflammation, oxidative stress and suboptimal nutrition. Strategies to prioritise HM volume in breast pump-dependent mothers of premature infants and evidence-based techniques to ensure that premature infants receive the highest possible quantity of HM during the NICU hospitalisation (NICU dose) are detailed. Evidence-based and best practices that facilitate the transition from gavage to at-breast feeding are also reviewed.

16.2 Human Milk Feedings for Premature Infants: Health Outcomes, Costs, and Mechanisms of Protection

16.2.1 Health Outcomes of HM Feedings

Several studies support the effectiveness of HM in reducing the risk, incidence, and/or severity of NEC, sepsis, ROP, and CLD, four primary acquired NICU morbidities that are serious, potentially handicapping, and costly in premature infants [1][17], [22]. However, until recently this impact was not fully appreciated due to several limitations in the available literature [19], [20], [28], including:

  • Lack of distinction between receipt of HM and donor HM feedings (e.g., HM feedings included both donor and own mother’s HM)

  • Inconsistent study samples that included mixtures of premature infants with low birth weight (< 2,500 g birth weight), very low birth weight (VLBW; < 1,500 g), and/or extremely low birth weight (< 1,000 g birth weight)

  • Retrospective methodologies and secondary analyses of studies that were not designed to measure outcomes of HM feedings

  • Use of inexact measures of the amount (dose) and timing (exposure periods) during which infants received HM feedings

Recently, a team of investigators has addressed these limitations in the large prospective Longitudinal Outcomes of Very Low Birthweight Infants Exposed to Mothers’ Own Milk (LOVE MOM) cohort study, which was designed specifically to measure health outcomes and cost of HM feedings for very low birth weight (VLBW) infants. (National Institutes of Health [NIH] grant NR010009) [29]. The LOVE MOM cohort enrolled 430 VLBW infants between 2008 and 2012 (95% of eligible infants), the majority of whom were born to minority (52% Black, 27% Hispanic), low-income (70% Supplemental Security Income, Women, Infant Child [WIC]-eligible, 185% of the poverty level) mothers [19], [27], [30]. A unique feature of the LOVE MOM cohort is that the dose and exposure period of HM feeding was measured prospectively by calculating the total amount of HM and the total amount of commercial formula (in mL) received by each infant daily during NICU hospitalisation [20]. Of the 430 infants, 98% received some HM (range 3–28, 229 mL during NICU hospitalisation), 76.8% and 59.7% of the cohort receiving exclusive HM during the Days of Life (DOL) 1–14 and 1–28 exposure periods, respectively. Over the NICU hospitalisation, 48.6% of all enteral feedings consisted of HM [19], [20], [27]. Donor HM was not used during this study, so all non-HM consisted of commercial formula, and HM was fortified with a commercial bovine powder [4], [8].

In the LOVE MOM cohort, high-dose HM feedings during three critical exposure periods during NICU hospitalisation significantly reduced the risk of NEC, sepsis, and CLD and their associated costs [4], [8], [20], [31]. During exposure period DOL 1– 14 any amount of formula (e.g., < 100% of HM feeding) increased the risk of NEC three-fold. After controlling for costs due to NEC risk, each additional mL of HM received during DOL 1–14 decreased the total NICU costs by US $534 [8]. During exposure period DOL 1–28 each additional 10 mL/kg/ day of HM feeding reduced the risk of sepsis by 19% [4]. The difference in sepsis-related NICU costs between the highest (≥ 50 mL/kg/day) and the lowest (< 25 ml/kg/day) HM doses for exposure period DOL 1–28 was US $31,514 (in 2010). For CLD, every 10% increase in HM enteral feedings during NICU hospitalisation up to 36 weeks post menstrual age (PMA) reduced the risk of CLD by 9.5%; CLD was associated with an additional US $41,929 in NICU costs [15]. In addition to increasing NICU cost of care, NEC, sepsis, and CLD predispose VLBW infants to neurodevelopmental delay and other lifelong health care problems and their associated costs [22], [32],[33],[34],[35],[36],[37],[38],[39],[40]. Thus, feeding HM during NICU hospitalisation represents a safe and effective strategy to reduce lifelong health problems and their associated costs in VLBW premature infants.

At the time of this writing, 251 LOVE MOM infants who had reached 20 months of age, corrected for prematurity (corrected age, CA) were evaluated to determine the impact of NICU HM dose on subsequent neurodevelopmental outcome. After controlling for known confounders, each additional 10 mL/kg/day of HM during NICU hospitalisation translated into increases of 1.37, 1.48, and 1.44 for scores on cognitive, language, and motor evaluations, respectively [16]. Overall, differences between the lowest and highest NICU HM-dose groups (HM 2 ± 2% and HM 98 ± 5% of total enteral feed volume, respectively) were clinically significant, with 5–10-point differences (1/3– 2/3 of standard deviation) across cognitive, language, and motor outcome measures. These outcomes were noted despite the fact that infants in the highest HM quintile grew more slowly during NICU hospitalisation and were significantly more likely to be classified as extra-uterine growth retardation (EUGR; weight at 36 weeks < 10th percentile for weight) as compared to subjects in the lowest HM quintile [16].

The LOVE MOM cohort provide meticulously measured, prospective evidence for the positive impact of high NICU HM dose on neurodevelopmental outcome in NICU-hospitalised VLBW infants [4], [20], [22], [41],[42], [43], [44], [45], [46]. It is likely that high dose HM feedings received during critical periods during NICU hospitalisation impact on neurodevelopmental outcome through both direct mechanisms (such as nutritional and bioactive substrates) that facilitate brain growth and development, and indirect mechanisms (including reducing the risk of NEC, sepsis, and CLD) that contribute to neurodevelopmental and chronic health problems [16], [47], [48].

16.2.2 Cost of Human Milk Feedings

A primary barrier to the achievement of higher NICU HM doses in premature infants is lack of investment in clinical resources that target HM provision and feeding during NICU hospitalisation [18], [19], [21], [27], [43], [44]. These resources include maternal access to hospital-grade electric breast pumps for use in the NICU and at home, and adequate HM storage containers and space (e.g., food-grade storage containers, refrigerators, and freezers). They are required to store all pumped HM in the hospital under temperature controlled and tamper-proof conditions. Most importantly, breast pump-dependent mothers of NICU infants need access to NICU lactation specialists who have expert skills in lactation physiology following premature birth; breast pump use and other lactation technologies (e.g., measurements of HM calories and HM intake during breastfeeding); safety of maternal medications and associated health conditions; and HM expression manipulation and measurement technologies. Such care facilitates adequate infant growth without unnecessary addition of and/or replacement with commercial formula [18], [19], [27]. These necessities are relatively inexpensive when compared with the cost of acquired NICU morbidities for which HM is protective [21].

However, removal of barriers to providing and using HM also requires upfront investments in products and personnel. These are often seen as superfluous by administrators unless they are linked cogently to the reduction in overall NICU and societal costs. Economic data from the LOVE MOM cohort indicate that the institutional costs of providing HM are lower than providing either donor HM or commercial formulas [21], [22], [43], [44].

16.2.3 Protective Mechanisms of HM for Premature Infants

Multiple nutritional components and bioactive mechanisms in HM act synergistically to provide protection for premature infants whose organs are in immature stages of development and susceptible to damage. Such damage may be caused by inflammatory stimuli, oxidative stress, and suboptimal nutrition, which are common in the NICU [15], [19], [39], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63]. The impact of these noxious stimuli continues to contribute to and/or program abnormal organ growth and development long after the initial insult [48], [51], [52], [59], [62], [63], [64], [65], [66], [67], [68]. A key mechanism afforded by HM feeding is provided by the gut and its microbiome and metabolome, which contribute early protective programming, and reparative processes to multiple body organs and physiological pathways [39], [48], [49], [51], [52], [60], [61], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78]. Gut dysbiosis up regulates inflammatory cytokines and facilitates translocation of pathogenic bacteria and their pro-inflammatory toxins from the gut lumen to the underlying gut mucosa. Thence, these proinflammatory cytokines migrate, potentially altering the structure and/or function of organs (e.g., brain, lung, and eye) and pathways (e.g., immunomodulatory pathways) during critical developmental stages [39], [48], [50][52], [60], [70], [72][75], [77], [78], [79], [80], [81], [82], [83].

16.2.4 Protection via HM Feedings

HM feedings provide unique nutritional substrates and bioactive components that stimulate and/or program optimal growth and development of immature organs and physiological pathways while preventing/moderating biological insults from inflammation, oxidative stress, and suboptimal nutrition [18], [19]. Early HM (DOL 1–28) from mothers who deliver prematurely has high concentrations of bioactive components [51], [72][75], [84], [85],[86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98] that:

  • Stimulate growth, differentiation, and reparative functions in the gut epithelial border

  • Decrease intestinal permeability and thus translocation of bacteria to the underlying mucosa

  • Down regulate inflammatory and oxidative stress processes

Large HM doses thereafter likely have an even greater impact on post-NICU health and neurodevelopmental outcomes because they provide:

  • Probiotic (eg., live bacteria via the HM microbiome) [51], [99], [100], [101], [102], [103], [104], [105], [106] and prebiotic (food for commensal bacteria via HM oligosaccharides) activity [101], [107], [108], [109], [110], [111]

  • Pattern recognition receptors (Soluble CD14) that facilitate bacterial-enterocyte crosstalk in the immature gut [112], [113], [114]

  • Potent anti-inflammatory (interleukin 10, lactoferrin, glutamine) [88], [115],[116], [117] and antioxidant [87], [89], [118], [119] functions

  • Specific substrates for brain growth and myelination, including lactose and triglycerides for energy, fats that optimise myelination (cholesterol, long chain polyunsaturated fatty acids), and insulin-like growth factor-1) [58], [120], [121], [122], [123]

Some of the more than 200 HM oligosaccharides as well as HM stem cells are thought to have neuroprotective and neurodevelopmental activity [105], [125]. Recent magnetic resonance imaging studies of term [126] and preterm infants (born 1982–1985; Lucas cohort) studied during adolescence [124] revealed a dose-response relationship between the lifetime HM dose and brain white matter development, especially for males. Thus, HM appears to play a strong biologic role in the shaping of childhood health and neurodevelopmental outcomes in former premature infants.

16.2.5 Donor HM as a Supplement/ Substitute for HM

Both the American Academy of Pediatrics (AAP) and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) have recommended the use of donor HM when HM is not available [127], [128]. However, compared to HM for VLBW infants, the nutritional and bioactive deficiencies in donor HM are sizeable, and are demonstrated most dramatically in slower growth rates and greater proportion of NICU morbidities [6], [23], [129]–[136]. The strongest empirical evidence for the efficacy of donor HM is its associated reduction in the risk, incidence, and severity of NEC in premature infants [23], [129]– [131], [136]–[138]. However, it is unclear whether this is due to donor HM efficacy or the avoidance of bovine-based products (for which donor HM is a substitute), especially during the early weeks post birth [1], [8], [19], [24], [25], [129], [138], [139]. There is inconclusive published evidence for the impact of donor HM on sepsis, CLD, and later neurodevelopmental outcome [6], [23], [129], [135], [136], [138]. However, a limitation in nearly all donor HM studies is that most infants have received either donor HM or formula as a supplement to HM, and the dose and exposure period of HM has not been measured or standardised [6], [19], [23], [129], [138]. Thus, the infant’s initial and/or partial exposure to HM may minimise the additional impact of donor HM versus formula.

A nearly universal concern of donor HM feeding is the slower growth rate in cohorts of donor HMfed premature infants versus HM-fed and formulafed premature infants [6], [23], [131], [134]. Whereas the most common clinical solution for slower growth is more aggressive fortification, particularly earlier introduction and longer use of high exogenous bovine protein concentrations, no long-term outcome data exist to indicate that this is the best practice [19], [23], [140]. Additionally, several differences between donor HM and HM potentially affect growth rate but have been given little clinical consideration, including:

  • Stage of lactation, especially with respect to adipokine concentrations and protein type [73], [114], [141]–[150]

  • HM following preterm versus term birth [91], [92], [97], [141], [151]

  • HM collection, storage, and handling procedures except pasteurisation [19], [105], [125], [152]– [155]

  • Specific mother-infant mismatch between specific HM components[156]

  • The different effect from HM of donor HM on infant digestion processes such as fat absorption that influence growth [157]–[159]

Overall, the evidence suggests a positive impact of donor HM as a supplement or replacement for HM during early NICU hospitalisation when premature infants are at the greatest risk of NEC. However, additional short- and long-term outcomes of donor HM feedings remain inconclusive.

This evidence underscores the importance of prioritising mothers’ own HM in the NICU, including articulating the differences between donor HM and HM to infants’ families as they make feeding decisions. Second, the evidence indicates that donor HM and HM should not be included in the same outcome metric (e.g., HM feeding that includes both milks) for research and quality improvement initiatives. The outcomes for these two feeding regimens are not the same and the combined metric likely underestimates the impact of HM alone on short- and long-term outcomes for premature infants.

16.2.6 Summary – Human Milk Feedings for Premature Infants

HM provides the premature infant with protection from the common NICU stressors of inflammation, oxidative stress, and suboptimal nutrition; reduces the risks of NEC, sepsis, CLD, and ROP; and predicts 20-month CA neurodevelopmental outcome in a dose-response manner. This impact is likely due to the interaction and synergy of multiple HM components, many of which are concentrated more highly and/or function more selectively in HM of mothers who deliver prematurely. Donor HM does not provide these same outcomes for reasons that extend beyond pasteurisation. Priorities in the NICU should focus on the channelling of resources into programmes that promote initiation and maintenance of established lactation in mothers of premature infants. As a first step, messaging for families in the form of talking points about the importance of HM should be evidence based and standardised so that consistent, factual information is shared by health care providers [18], [19], [27], [160]–[162]. A sample of such talking points is shown in ▶Table 16.1.

▶Tab. 16.1 Sample messaging and talking points to share evidence about the importance of human milk feedings with families of premature infants in the NICU.


Talking Points


Making the Decision to Provide Own Mothers’ Milk

  • Your baby will need your milk as a part of his or her overall treatment plan

  • Receiving your milk reduces the chances that he or she will develop common complications of prematurity, such as infections and bowel disease

  • Several studies indicate that mothers of premature infants do not feel guilty, pressured or coerced by a proactive message from physicians and nurses about the importance of HM [27], [160], [162], [228]

  • Clarifying “reducing the chances” versus “benefits of human milk” nomenclature most accurately reflects the research findings about outcomes of HM for premature infants [18], [27]

Why is my milk so important for my baby?

  • The milk mothers make in the first few days after birth, called colostrum, provides many special substances that your baby’s intestines need to grow and develop, and that help their immune systems to develop to fight infection

  • We are also concerned about feeding formula during the early weeks after birth. Several studies suggest that formula increases the chances that premature babies will develop complications

  • Premature babies have not developed the same defenses against infection and other diseases as full term babies

  • Premature infants immature body organs and immunomodulatory and metabolic pathways are vulnerable to inflammation, oxidative stress, and nutritional deficiencies [18], [48], [50], [51], [53], [341]

  • Mothers who deliver prematurely produce HM with higher concentrations of many of the protective components (e.g., lactoferrin, and secretory immunoglobulin A, interleukin-10) that down regulate inflammatory processes. This is especially true of maternal colostrum and transitional HM [18], [19], [91][93], [95], [96], [99], [148]

  • Bovine formula exerts a separate detrimental impact via several mechanisms, including: greater and prolonged post-birth intestinal permeability, direct cytotoxicity, and gut dysbiosis [24][26], [139], [154], [342], [343]

HM = human milk, NICU = neonatal intensive care unit. ® Rush Mothers’ Milk Club, 2016. All rights reserved

16.3 Prioritising Initiation and Maintenance of Established Lactation in Mothers of Premature Infants in the NICU

Mothers of premature infants confront multiple challenges when initiating and maintaining lactation during their infants’ NICU hospitalisation [27], [163]–[166]. Whereas many of these challenges such as maternal health status and birthrelated complications are unmodifiable, the lack of evidence-based practices also places these vulnerable mothers at risk for establishing an inadequate HM supply [27], [163]–[167]. Lactation care in the NICU is a specialty practice area. It should be provided by health care providers with expertise in the management of breast pump dependency and use of other lactation aids (e.g., breast-shield sizing, HM analysis technologies, test weighing, and nipple shields), which facilitate pumping and HM feeding [19], [27], [168]–[172]. Additionally, mothers of NICU infants need specific information and guidelines about their own health conditions and medications that impact on HM provision and feeding [18], [27]. Although various models for providing NICU lactation care have been proposed, three have been implemented, evaluated, and disseminated in the research literature:

  • The Rush Mothers’ Milk Club, which incorporates breastfeeding peer counsellors (former NICU parents themselves) as primary lactation care providers [27], [173]–[176]

  • The Nurse Resource Model, which expands the role of the bedside NICU nurse to expert lactation care provider [168], [172], [177]

  • The NICU Baby Friendly 10-step model that is based on the original World Health Organization criteria [178]

16.3.1 Breast Pump Dependency

Mothers of NICU infants are completely breast pump-dependent. This means that the breast pump rather than the infant regulates the lactation processes of HM removal and mammary gland stimulation, which are critical to continued HM production [179]. Even after at-breast feeding is initiated in the NICU and continued post-discharge, these mothers remain partially breast pump-dependent (i.e., the breast pump remains the primary regulator of lactation) until the infant consistently takes all daily feedings at the breast effectively and efficiently; this is usually at 40–44 weeks postmenstrual age [179], [180]. These mothers therefore need access to a hospital-grade electric breast pump that is effective, efficient, comfortable, and convenient, and which offers simultaneous versus serial pumping, variable sucking rates, rhythms and pressures, and custom-fitted and warmed breast shields [18], [166], [181]– [192]. These criteria, the underlying evidence, and specific recommendations about individualising breast pump technology to both the degree of breast pump dependency and lactation stage are reviewed elsewhere [179].

A major barrier for many mothers is that public and private insurance plans and public nutrition programmes do not consistently provide or reimburse hospital-grade breast pump rental costs, despite a physician order of HM feedings for a NICU infant [18]. Instead, less costly manual or doubleelectric personal pumps that do not meet the abovementioned criteria for effectiveness, efficiency, comfort, and convenience are substituted; as such, mothers experience problems with establishing and maintaining an adequate HM volume [179]. A series of studies has examined maternal and institutional costs of providing HM for VLBW infants, and reviews have compared the upstart costs of providing HM with the costs incurred for morbidities that are potentially preventable with HM feedings [21], [22], [43], [44], [193], [194]. These studies have consistently shown cost savings when providing mothers with hospital-grade electric pumps for use in the home versus purchasing donor HM or commercial formula [21], [43], [44]. Thus, substantial evidence exists to support the institutional or other third-party payment for hospital-grade electric breast pumps for breast pump-dependent NICU mothers [179].

16.3.2 Strategies to Prioritise Established Lactation for Breast Pump-Dependent Mothers

Breast pump-dependent mothers of NICU infants have specific, predictable barriers to the initiation and maintenance of lactation, which infrequently occur for mothers with healthy term infants [27], [164], [165], [171], [179], [195]–[199]. These barriers, which have been detailed in individual studies [45], [164], [165], [173], [176], [196]–[201] and delineated in a recent review paper [179], can be divided into three stages of lactation: initiation, coming to volume, and maintenance of established lactation. A brief overview of these stages and common barriers is provided below.

Early lactation: initiation and coming to volume

The initiation of lactation coincides with the closure of tight junctions in the mammary epithelium [202]–[204], a process that is disrupted and/ or delayed by preterm and/or complicated birth [27], [197], [198], [205], [206], lack of exposure to human infant-specific sucking patterns [166], delayed breast pump use [165], [196], early hormonal contraception [207], [208], and prolonged hand expression in the absence of breast pump use [167].

Coming to volume refers to the lactation stage between the onset of lactogenesis II and the establishment of a threshold HM volume, typically ≥ 500 mL/day [27], [179]. This transition heralds the autocrine control of lactation [166], [202], [209]–[213] via the suckling-induced prolactin surge [214]–[217] and feedback inhibition of lactation [210], [218]–[220]. It is fraught with problems for even healthy mothers and infants [18], [166], [202], [221], [222]. Coming to volume in a breast pump-dependent mother with a NICU infant is further complicated by maternal stress, fatigue, pain, lack of clarity about HM volume targets, incorrect type/use of the breast pump (e.g., suction pressures, frequency, and pumping duration), and improperly-fitted breast shields [27], [179].

Furthermore, the early post-birth stages of initiation and coming to volume represent critical periods for the programming of lactation structures and functions, making it difficult or impossible for mothers with low HM volume to “catch up” after these critical periods have passed [27], [165], [167], [179], [196]. All available evidence indicates that the first 14 days post-birth should be prioritised by NICU staff with proactive interventions to prevent or detect these common problems.

During these early lactation stages, a major barrier to adequate HM feeding is that mothers do not receive information about the importance of establishing a threshold HM volume of ≥ 500 mL/ day during the first 14 days post-birth when programming of lactation structures occurs. Nearly all NICU infants, born either prematurely or with medical/surgical complications, require only small HM feedings during this time; mothers are therefore able to provide exclusive HM feedings despite pumping small HM volumes. However, as infants’ conditions improve and they receive the customary 150–180 mL/kg/day of HM, the mothers’ HM volumes are no longer sufficient; these insufficiencies often manifest at 4–6 weeks post birth [27]. It is likely that these HM insufficiencies originate in the initiation and coming to volume stages because mothers do not have the necessary information about HM volume targets to help them achieve their HM feeding goals [27]. Whereas mothers with healthy term infants who feed on cue do not need to worry about HM volume targets because their infants create the HM demand, mothers with NICU infants must create HM demand with the breast pump. Mothers of NICU infants therefore need to understand that there are two HM volume targets: one that is sufficient for exclusive HM feedings when infants receive small HM volumes (e.g., as little as 100 mL/day), and the other that is sufficient to protect and program long-term lactation (i.e., ≥ 500 mL/day by the end of DOL 14) [27]. Published monitoring tools and parent education sheets about this important concept are summarised in ▶Table 16.2.

Maintenance of established lactation

Several recent reports highlight the fact that increasing numbers of mothers of VLBW infants begin providing HM for their infants, but that significantly fewer are still providing exclusive or partial HM at the time of NICU discharge [20], [163], [199], [223]–[226]. It is well known that mothers of preterm and other NICU infants often change their decision from using formula to HM after conversations with healthcare providers [160]–[163], [227], [228]. They also do not plan to breastfeed long-term [160]–[163]. Regardless, the majority of mothers do not meet their self-stated goal to provide partial or exclusive HM at the time of NICU discharge. Few evidence-based findings inform this worldwide outcome [20], [163], [199], [223]– [226], even in NICUs that prioritise support for HM and breastfeeding [20], [27], [163], [199], [223]– [226]. It is likely that long-term breast pump dependency, maternal stress and fatigue, lack of access to hospital-grade electric breast pumps, having an infant who is no longer critically ill, insufficient support from family and friends, and inconsistent advice in the NICU all play a role in these mothers’ discontinuation of HM provision.

▶Tab. 16.2 Tools to monitor human milk volume for breast pump-dependent mothers of NICU infants



Maternal goals for providing HM in the NICU

  • Clarifies and communicates maternal goals for type of milk feedings (exclusive, partial, no HM) for NICU infants on a week-by-week basis and the method (exclusively at breast, exclusively pumped HM in a bottle, mixture of HM from breast and bottle) by which the want to provide HM at the time of NICU discharge

  • Denotes changes in HM feeding goals over the course of the NICU and alerts NICU staff to mothers at risk for not achieving their goals

Coming to Volume assessment tool for breast pump-dependent mothers in the NICU

  • Succinct checklist that monitors physiologic changes that coincide with the initiation and coming to volume stages of lactation for mothers who are at risk for delayed lactogenesis and who are breast pump-dependent

  • Identifies irregularities so that they can be quickly triaged and managed to avoid long-term HM volume problems

“My Mom Pumps for Me!” HM Volume Record and Diary

  • Convenient and engaging HM volume diary that helps NICU mothers and staff track pumping volumes for the right and left breasts separately, and time spent per pumping

  • Checkbook type insert pages permit journaling as well as the posting of decals that chronicle special events in the breastfeeding trajectory for NICU mothers, including 1st Kangaroo Care and 1st Tasting at the breast

  • Used to identify and manage HM volume problems with specific data (e.g., mLs pumped and time spent pumping) versus non-specific outcomes (e.g., “my milk is going down”)

HM = human milk, NICU = neonatal intensive care unit

Profound dislike of the pumping process and lifestyle inconveniences required to maintain an adequate HM volume during NICU hospitalisation are common in breast pump-dependent mothers [45], [164], [176]. These personal factors interact with events over the NICU trajectory, leading mothers to perceive that their HM given at a later time post birth is not as critical to their infants’ outcome as it is during the early post-birth period. These NICU events do not necessarily follow a logical progression, making it difficult to identify whether the maternal HM volume declined because of the clinical event. The following series of NICU events illustrates this phenomenon. When the infant is no longer critically ill and requires larger volumes of HM, the mother’s HM volume is no longer adequate for exclusive HM feedings. The infant is therefore supplemented with donor HM or preterm infant formula and tolerates it well. Once the mother observes that her convalescing infant grows, gains weight, and reaches milestones on donor HM and/or formula, she questions whether her dislike and inconvenience of pumping are worth the effort. When the mother’s HM volume further decreases, it is likely due to a reduction in pumping patterns and acceptance of a less ambitious goal for HM provision [45], [163], [176], [229].

It has been suggested that maternal (e.g., prenatal intention, motivation) rather than infant factors (e.g., weight, critical health status) are the primary drivers in the decline in HM provision at NICU discharge [225]. It is clear that messaging by NICU care providers impacts on the mothers’ decisions to initiate lactation. However, researchers have theorised that mothers revert back to their original prenatal intention to formula feed their infants when faced with the challenges of maintaining an adequate HM volume for weeks at a time, while observing their infant thrive on donor HM or formula [163], [230], [231]. Further research is needed to develop and test strategies that extend early messaging to include self-efficacy and longer-term health outcomes of HM provision for NICU infants and their mothers. An additional priority is the design of breast pumps that optimise efficiency (e.g., the total number of minutes per day spent pumping) in breast pump-dependent mothers without compromising the pump’s effectiveness, comfort, and convenience.

16.3.3 Summary – Prioritising Initiation and Maintenance of Established Lactation

Breast pump-dependent mothers with NICU infants face numerous barriers to the initiation and maintenance of established lactation that are not experienced by mothers with healthy infants. Such barriers require management by specialists in NICU lactation care. Of particular concern is the early post-birth period, which includes the initiation and coming to volume phases of lactation, when mothers frequently receive inappropriate advice and equipment that compromises long term HM production. Significant evidence exists to mitigate many of these problems but is not routinely implemented due to resource and ideological concerns. The maintenance of established lactation through to NICU discharge is a research priority, as is the design of more efficient hospital grade electric breasts so that pumping is not so arduous for mothers of NICU infants who are breast pump-dependent for long periods.

16.4 Managing Human Milk Feeding in the NICU

Several studies provide evidence about best practices for collecting, storing, handling, and feeding HM in the NICU setting [19], [27], [169], [170], [232], [233]. However, the majority of these findings have not been integrated into comprehensive HM feeding programmes specific to NICU infants. This slow translation from research to practice has been influenced by a lack of scientific knowledge about HM by NICU care providers and institutional investment in products to support best HM feeding practices. This section reviews evidence and strategies for managing the variability in pumped HM, and principles for the safe handling of HM in the NICU setting.

16.4.1 Variability in Pumped HM in the NICU

The marked within and between-mother variability in the composition of pumped HM for NICU feedings has been studied extensively [18], [234]– [238], and a recent review paper has detailed clinical techniques to identify and manage this variability [19]. Three primary causes of clinically significant variability in the composition of pumped HM in the NICU are stage of lactation, degree of breast fullness immediately before HM removal, and the completeness of breast emptying during pumping [19]. A basic understanding of these principles can help resolve most growth and feed tolerance problems related to HM feedings in the NICU.

Stage of lactation

Major within-mother HM compositional changes occur between lactation stages [19]. Colostrum, secreted prior to the closure of paracellular pathways in the mammary epithelium, is almost exclusively high molecular weight developmental and protective proteins. It includes a myriad of growth factors, immunoglobulins, cytokines, lactoferrin, lysozyme, anti-inflammatory agents, and anti-infective components (e.g., live cells, probiotic HMborne bacteria, and oligosaccharides) [84], [97], [99], [105], [107], [144], [239], [240]. As such, colostrum is more like amniotic fluid than mature HM [83], [239], [241]. In contrast to mature HM, colostrum contains only traces of casein and lactose, and a relatively high sodium concentration [239]. A study of HM transcriptome showed that immune proteins are upregulated during colostrum and transitional HM secretion, whereas nutritive proteins are upregulated later in lactation [148]. As the tight junctions in the mammary epithelium close, coinciding with the onset of lactogenesis II (secretory activation), HM composition changes dramatically, with higher lactose and lower sodium concentrations [239]. Total HM protein remains elevated in all mothers during the first month of lactation, but especially in those with premature infants, primarily due to concentrated developmental and protective proteins [88], [91][93], [97], [142].

Colostrum is extremely important for NICU infants who have immature or compromised gastrointestinal tract development, are immunosuppressed, and/or are at risk of NEC [18], [19], [47]. The many growth factors in colostrum work synergistically to stimulate rapid growth and differentiation of the intestinal epithelial border, catalyse the closure of tight junctions in the gut, and may selectively effect the growth of other body organs [72][75], [91], [92], [242]–[246]. Secretory IgA, lactoferrin, and other bioactive components provide barrier protection and down regulate inflammation and oxidative stress responses [87], [119], [242], [244]–[246]. Specific colostral cytokines appear and disappear in a temporal manner, suggesting that the order of colostrum feeding is of physiologic significance for the infant [18], [247]. Thus, priority should be given to collecting, labelling, and storing colostrum so that it can be fed in the order that it is pumped by NICU mothers (procedures are detailed elsewhere) [18], [19], [27].

Several non-randomised and one randomised study have demonstrated the safety, feasibility, and preliminary efficacy of colostrum administered via the oropharyngeal route [42], [248]– [250]. Colostrum should be given first as a feed, with increases in feed volume per NICU protocol. Colostrum should not be fortified using bovine products due to their effect on bioavailability of the protective components in HM [47]. Of particular concern is lactoferrin, a potent anti-infective and anti-inflammatory cytokine that is most highly concentrated in preterm colostrum and transitional HM, and that is inhibited in the presence of exogenous iron supplementation [88], [244], [251]–[255]. HM fortification, while standard of care for most VLBW infants, should be delayed for as long as feasible during feeding with colostrum to enable maximum growth, colonisation, and protection to the fragile premature infant intestinal tract [19].

Breast fullness immediately before HM removal

Healthy term infants who breastfeed exclusively demonstrate remarkable variability in the total daily amount of HM consumed, daily breastfeeding frequency, and amount of HM consumed from each of the two breasts (including over and underproductive breasts) [256]–[258]. Whereas this variability is normal, it can be problematic in the NICU where infants are typically fluid-restricted, have high caloric needs, and are prone to immaturity-related feed intolerance [19]. A principle factor driving the total caloric content in pumped HM is the degree of maternal breast fullness immediately before HM removal [256]. Basically, when a mother pumps a very full breast, a larger volume of HM is removed but it contains less lipid and fewer calories, and has a relatively greater proportion of calories to lactose, compared to a less full breast [19], [256]. Unlike the mother with a healthy infant who breastfeeds according to infant demand, the NICU mother schedules pumping sessions around her other daily activities. Long stretches between pumping to enable sleep or return to employment outside the home can result in pumped HM that is of high volume, low calorie, and has low-lipid and relatively high lactose concentrations [19].

In the term infant, the HM removed after a long inter-pumping interval is balanced by higher lipid HM over the course of the day when the breast is not filled to capacity [256]–[258]. However, for the NICU infant, a single pumping of low-calorie, lowlipid, high-lactose HM from a full breast may provide sufficient volume for several sequential feedings over the course of a day [19]. The clinical consequence of this common NICU scenario is slow weight gain and occasional symptoms of feed intolerance, which often lead to formula supplementation or use of more highly concentrated exogenous HM supplements [19]. This problem is easily preventable or correctable with appropriate parent education, HM diaries, and creamatocrit measures [19], [27], [236], [237].

Completeness of breast emptying during pumping

The lipid and calorie contents of HM increase dramatically over the course of feeding or pumping; with low-lipid HM flowing early in the pumping (fore-milk) and high-lipid HM flowing near the end of pumping (hind-milk) [19], [236], [237], [259]. However, the pattern of lipid release into HM is not strictly divided into two phases but is a continuum of increasing lipid content during HM removal [259]. Breast pump-dependent mothers can visualise HM flow from the breast, with the rate of flow decreasing over the course of HM removal (as lipid content increases) [19]. Mothers tend to stop pumping before removing high-lipid HM because they observe that the HM flow rate is slower than it was after initial milk ejection. Key to avoiding this scenario is to instruct mothers to pump until they no longer see HM droplets for 1– 2 consecutive minutes; a standardised pumping time (e.g., 10–15 minutes) does not reflect research about individual mothers’ HM flow rates and lipid release. In another scenario, a mother whose HM volume per pumping exceeds the receptacle into which she is pumping may store the pumped HM in serial receptacles as pumping progresses. This results in individual receptacles containing HM with markedly different lipid and calorie contents. Unfortunately, in the NICU, all receptacles of HM are typically fed to infants as if equivalent. Additionally, clinical case studies indicate that infant growth and feed tolerance may be affected by variable lipid and calorie contents of pumped HM following incomplete breast emptying [19].

16.4.2 Safe Handling of Human Milk in the NICU

Few NICU infants are able to consume exclusive HM feedings at the breast, so HM must be collected, stored, and fed via gavage infusion until the infant is able to breastfeed effectively and efficiently. Each of these handling processes compromises the nutritional and bioactive components in HM, and introduces the potential for microbial and environmental contamination [260]. Thus, the overarching priority for HM feeding in the NICU is to implement best practices that optimise preservation and delivery of nutritional and bioactive components in HM, while minimising the risk of contamination [19]. This section reviews the evidence for fresh versus frozen or pasteurised HM feedings, guidelines for care of breast pump and HM storage supplies, and best practices for HM administration via gavage infusion.

Fresh versus frozen HM

The nutritional and bioactive components in HM are optimally preserved, and microbial contaminants are minimised when freshly pumped HM (i.e., never refrigerated or frozen) is fed in the NICU [19], [47]. Freshly pumped HM is exceptionally robust with regard to bioactivity of live cells that phagocytise bacteria in the HM, and can easily be kept at room temperature for up to 4 hours post expression [261]. Most HM components are preserved with refrigeration (4 °C), and unfortified HM can be refrigerated for at least 96 hours post collection without significant changes in composition or microbial growth [262]. Whereas many bioactive components in HM are partially preserved with freezing (–20 °C), live cells (including stem cells, and macrophages that phagocytise potential pathogens) are completely destroyed [261]. Freezing also disrupts the structure of the HM lipid globule membrane, making thorough mixing of thawed HM more difficult [262]. Furthermore, freezing HM does not inactivate the HM lipases, so free fatty acid concentrations are frequently higher and pH may be lower in frozen-then-thawed HM than in fresh HM [259], [264]. Once frozen, HM must be thawed and warmed prior to feeding. Studies have addressed the potential for bacterial growth in previously-colonised HM during these processes, especially when water rather than dry heat is used for warming [264]–[266]. While eradicating most bacteria and viruses, pasteurisation of HM also destroys or markedly reduces the concentration and/or bioactivity of multiple clinically significant HM components including the HM microflora; it should therefore not be used routinely for own mother’s HM in the NICU [23], [135], [267] - [269]. Thus, several lines of evidence support the prioritisation of feeding fresh, unfrozen HM in the NICU, with frozen (then thawed and warmed) HM as a second-best practice [18], [19], [47], [270].

Storage of HM

In the NICU setting, all refrigerated and frozen HM should be stored in industrial-quality refrigerators and freezers that are continuously monitored, temperature controlled, and connected to a central monitor that alarms when HM safety is compromised. However, it is not uncommon for families of NICU infants to be told to keep HM at home due to lack of appropriate storage facilities (as a consequence of lack of NICU investment). This practice places both infant and institution at risk because there is no quality control of in-home storage conditions. Families have been known to store pumped HM in the trunk of the family car during winter months, and at family or friends after journeying on public transport for several hours in summer months. The basic safety issue of uncontrolled HM storage conditions is easily preventable by avoidance of HM storage at home.

Care of breast pump supplies and HM storage containers

Nearly all NICU mothers use a breast pump to remove HM; these pumps and their accompanying collection kits must be cared for hygienically to reduce the risk of HM-borne bacteria [271]. In contrast to older model electric breast pumps that were sources of NICU infection outbreaks [272], [273], all newer hospital-grade electric breasts are designed for multiple users and have internal safeguards that prevent bacterial transfer between mothers. However, when shared among NICU mothers, the exterior pump surface and other areas that come in direct contact with the pump kit should be thoroughly disinfected between users. NICU mothers can disinfect the breast pump just before use provided they are properly educated in this practice and have a visual reminder attached to the breast pump (▶Fig. 16.1). Non-hospital-grade pumps for personal use should not be shared among mothers; this is especially important when pumping HM for immunocompromised NICU infants [271].

▶Fig. 16.1

(a) Sample laminated instruction card for mothers to use in the NICU (neonatal intensive care unit) to disinfect the exterior of the breast pump prior to use. (b) The nurse shows the card, attached to the breast pump, to the mother as she demonstrates the disinfection procedure. (® Rush Mothers’ Milk Club, 2016. All rights reserved)

HM collection containers and tubes (e.g., the pumping kit) should not be shared among mothers unless thoroughly sterilised between users in a designated hospital area. In most of today’s NICUs, mothers receive and are expected to care hygienically for a single-user breast pump kit. To ensure quality cleansing, the NICU should provide the mother with necessary equipment (e.g., standardised dishwashing detergent), a demonstration of kit-cleaning procedures, and a back-up visual guide such as an education sheet (▶Fig. 16.2). To reduce the risk of contamination, pumping HM into a combination collection kit storage container is an excellent alternative to the transfer of HM from one container to another. However, care must be taken if the mother’s HM yield from an individual breast exceeds the capacity of the storage container. If not instructed otherwise, the mother would pump sequential containers of HM, each with a successively higher lipid and calorie content [19]. A recent paper reports evidence-based guidelines for decontamination of breast pump collection kits in the hospital and home, and is an excellent resource for NICU policies and procedures [271].

▶Fig. 16.2

Sample parent education sheet that reinforces staff teaching about proper care of breast pump collection equipment. (® Rush Mothers’ Milk Club, 2016. All rights reserved)

The NICU should provide mothers with an adequate quantity of sterile, food-grade containers for HM storage. These containers should be easy to use by NICU staff, particularly if HM feedings are prepared at the bedside by NICU nurses. Specifically, the containers should have a lid that is easily removed and replaced without contaminating either lid or HM, be durable to prevent puncture or damage during storage, and have an external surface that allows firm adhesion of identification labels during handling. Furthermore, the nurse should be able to mix the HM thoroughly and to withdraw the prescribed feed volume with a sterile syringe. In the Rush Mothers’ Milk Club programme [19], four separate sizes of containers (11 mL for colostrum, 60 mL, 120 mL, and 240 mL) are used to minimise storage space and to accommodate different volumes of pumped HM. Larger storage containers are available to pool pumped HM over the course of a 24-hour period, and the safety of this practice has been demonstrated [238]. HM for NICU infants should never be collected or stored in commercially-purchased plastic bags that are unsterile and/or non-food grade [274]. Even food-grade HM storage bags present limitations in the NICU because of the difficulty in mixing HM lipids (that adhere to bag crevices) in and maintaining sterility during HM removal [274].

Routine culturing of HM samples

In the 1970s and 1980s, several original research reports documented the potential for HM as a source of bacterial contamination and/or bacterial growth in the NICU [272], [273], [275]–[279]. Bacteria potentially spread via mothers’ hands, contaminated breast pumps, kits and storage containers, nurses’ technique during feed preparation, and water-bath warming. Continuous gavage infusion, during which the already colonised HM was warmed and maintained at room and/or isolette temperatures for several hours, was found to be a particular risk [280]. While widely known that healthy term infants ingested an array of bacteria during breastfeeding [281], concern for immunocompromised NICU infants led to routine microbiologic surveillance of pumped HM in many NICUs [275], [276], [282]–[284]. However, this practice is not as effective in preventing HM contamination as is parent and nurse education about hygienic practices of caring for HM that is collected, stored, and fed artificially [284], [285].

Schanler, et al. [285] found that exposure to bacteria cultured from mothers’ pumped HM did not increase the infection risk in extremely premature recipients, leading to the conclusion that there is no clinical utility in routine microbiologic surveillance. These data are consistent with previous reports demonstrating that mother and infant can be exposed to a common microbe simultaneously. Thus, isolates in HM and infants do not guarantee that the mother was the source of the organism. Consequently, there is no scientific rationale for routine HM cultures in the NICU. Instead, data indicate that NICU resources should be invested in HM equipment such as waterless HM warmers and commercial freezers, and maternal education about hygienic practices for the care of pumped HM should be prioritised.

Options for handling and feeding pumped HM

Although maternal techniques for pumping and transporting HM are frequently assumed to be the primary source of HM contamination, multiple sources and handling procedures within the NICU introduce new contaminants or facilitate growth of existing ones. For example, once HM is received in the NICU, it is stored, thawed (if frozen), warmed, fortified with an exogenous commercial product, and administered artificially by intermittent gavage, continuous gavage, or bottle until the infant can consume feedings directly from the breast. Although substantial evidence exists for optimal procedures for each of these steps, they are more often informed by cost and tradition, and vary widely among individual NICUs [19], [286].

Currently, there are two overall approaches to HM handling in the NICU: Feedings are prepared (including fortification) either offsite by HM technicians and delivered to bedside nurses every 24 hours [170], [287], or at the bedside by the NICU nurse [18], [19]. Advantages of the former include: fewer health care providers handling HM and thus less variation in standardised practices; purported less misadministration errors (e.g., infant receiving HM from the wrong mother); and resource consolidation for cost-effectiveness. In contrast, the nurse’s mixing of HM at the bedside enables: customisation of specific HM collections to feed (e.g., colostrum, high-calorie hind-milk, and fresh versus frozen HM), which may benefit the individual infant; less inadvertent HM wastage; and the ability to add exogenous fortifiers to warmed HM immediately before feeding instead of up to 24 hours in advance of feeding. There are no data to indicate which method is superior; this can easily vary with the NICU size, bedside nurses’ education, and the basic NICU approach of standardisation versus individualisation of feedings.

Warming and thawing stored HM

Stored HM must be thawed and/or warmed before administration, and several studies indicate that use of a water bath presents an additional infection risk to HM handling in the NICU [265], [266]. Studies suggest that water bath heating of HM also results in variation of administration temperatures, some of which may be considerably below or above infant body temperature [264], [288], [289]. From a safety perspective, HM should therefore be heated without water and the administration temperature should be around body temperature for extremely premature infants (note that in such infants unwarmed oxygen and blood are considered inappropriate). For the smallest infants, HM feeds can be prepared an hour in advance and placed in the infant’s incubator (▶Fig. 16.3). This technique ensures waterless warming to a physiologic temperature. A randomised clinical trial of HM heating by a commercial waterless HM warmer versus the makeshift water bath demonstrated that the waterless warmer is safe and effective for warming and thawing HM in the NICU [264]. To reduce the impact on HM bioactive components and prevent marked increases in HM osmolality, exogenous bovine fortifiers should be added after HM warming and just before administration.

▶Fig. 16.3

The nurse has prepared the infant’s 2-hourly bolus feeding and is placing it in the incubator approximately 1 hour prior to feeding so that it can warm (without water) to approximately body temperature. (® Rush Mothers’ Milk Club, 2016. All rights reserved)

Fortification of pumped human milk

Most HM feedings for extremely premature infants will be fortified with an exogenous product of concentrated macro and micro-nutrients in powder or liquid form, added before feeding [290]. While there are many references to the inadequacies of HM fortification for this infant population [291], the indication for fortification largely depends on the infant managing to consume only a fraction of the average daily HM volume produced by the mother [19]. The distinction between inadequacy of HM versus limited volume of intake is important for NICU mothers; while encouraged to provide HM, mothers may also be told that their HM is inadequate for their infants. It is almost universally recognised that extremely premature infants need additional protein, calcium, phosphorus, and other nutrients, although there is no agreement as to when to initiate/terminate these supplements [290]. Central to this issue is the fact that commercially available bovine-based fortifiers interfere with the nutritional integrity and bioactivity of HM components [47], [119], [251], [292], [293]–[297], and that many of these HM components provide protection from NEC [19], [47].

From a clinical perspective it would make sense to delay the introduction of bovine-based supplements until full enteral HM feedings are well established, and the baseline lipid concentration is individualised to 55–60% of total calories [19]. An alternative perspective is based on the fact that extremely premature infants experience a period of marked nutrient deficiency immediately post birth (especially protein), and that protein deficiency may be linked to long-term neurodevelopmental delay [291], [298]. Although the latter perspective arises from observational studies [298] with one randomised trial reporting no beneficial effect of high-protein supplements during NICU hospitalisation [140], early and longer duration of fortification, especially with bovine protein, has become a widely accepted practice worldwide [127], [291], [299], [300].

One promising approach in this area is the use of supplements derived by concentrating HM protein and other components into a true HM-based fortifier. HM-based fortifier has demonstrated the potential to preserve HM components and bioactivity while providing additional macro- and micro-nutrients required by extremely preterm infants [129], [297]. The primary disadvantage to HM-based fortifiers is that they displace the mother’s own HM, which may be > 50% of the feed volume during early enteral feeds in extremely premature infants. From a pragmatic viewpoint, the HM-based fortifier displaces mother’s own HM with a pasteurised donor HM product. This product does not negatively affect the infant but reduces the early dose of mother’s own HM, which is linked with protection from NEC [1], [2], [8]. Randomised clinical studies that measure shortand long-term outcomes of the various feeding approaches are needed to clarify the best way to fortify early HM feedings for extremely premature infants [290].

Gavage Infusion rate of pumped HM

Considerable data indicate that HM feedings should be administered by intermittent rather than continuous gavage infusion. However, these data are frequently disregarded by clinicians who purport that continuous feedings are associated with fewer episodes of apnoea and bradycardia than intermittent feedings. Slow infusion and/or continuous gavage feedings trap HM lipids in the syringe and administration tubes, potentially resulting in the delivery of HM containing significantly fewer calories and lipids compared with baseline [155], [301], [304]. This may be even more pronounced when thawed frozen HM versus fresh HM is administered [303]. Over 24 hours, lipid losses can be sizeable and affect infant feed tolerance and weight gain. Every attempt should be made to shorten the duration of gavage HM infusion to the maximum safety point, particularly in extremely premature infants whose growth and feed tolerance are especially susceptible to this deficiency. This practice is in direct contrast to the non-evidence-based opinion of it being safer to administer feeding slowly. Feeding smaller volumes of HM every 2 hours via intermittent gavage for the smallest premature infants (e.g., < 1,250 g) may have physiologic benefits, and would solve the problem of lipid loss in slow infusion continuous HM feedings [305]. However, the main reason cited for not feeding frequent small volumes is nursing efficiency, e.g., the cost savings associated with less frequent gavage feedings may outweigh the benefits of physiologic stability and feed tolerance in extremely preterm infants [305].

An additional concern about feeding very slow flow continuous gavage HM infusion is that bacteria in already-colonised HM continue to increase over the course of infusion [280]. Depending upon the duration of continuous gavage feeding, bacterial load can be of concern, especially if the HM has been previously frozen thereby diminishing HM phagocytic properties [19]. If very slow gavage HM infusions are absolutely necessary, it is important to prioritise the feeding of fresh (never frozen) HM to optimise its bacteriostatic and bactericidal functions in already colonised HM.

16.4.3 Summary – Managing Human Milk Feeding

Best practices for the management of HM feedings in the NICU have been delineated in multiple research studies as well as summarised in state-ofthe-science reviews. These practices include the understanding and managing the variability in pumped HM that is fed in the NICU. HM should be fed to infants fresh, never frozen or pasteurised, as much as possible. Specifically, HM from the infant’s own mother should not be routinely pasteurised. All pumped HM should be stored in the NICU in commercial refrigerators and freezers that are temperature controlled and tamper proof, and practices that ensure breast pumps, collection containers, and storage containers meet hygiene standards must be implemented. HM should not be warmed in a water-bath prior to NICU feedings, and any fortification should be added immediately prior to feedings. Furthermore, feeding HM by intermittent rather than continuous gavage, as much as possible, especially in extremely preterm infants is advised.

16.5 Feeding at Breast in the NICU

Approaches to feeding at breast in the NICU vary widely and often reflect tradition, ideology, and feasibility more than evidence-based practices [27]. For example, some NICU clinicians still assert that breastfeeding is tiring for a small premature infant, or that it is impossible to accurately measure HM intake during breastfeeding, despite evidence to the contrary [306]–[310]. Other NICUs have focused on the ideology of banning bottles and using alternative feedings only, despite a lack of evidence that this approach facilitates at-breast feeding, infant feeding development, and/or parent satisfaction with the overall feeding experience [178]. From a feasibility perspective, mothers must be physically present in the NICU to feed at breast, which complicates exclusive breastfeeding particularly in countries without paid maternity leave and similar social support. Helping a mother feed a NICU infant at breast requires dedicated time and a specific skill set on the part of the nurse or lactation specialist; this assistance is usually among the first to be discontinued with NICU budget cuts. Mothers may hear that bottle feedings will hasten infant discharge, and so be reluctant to feed at breast in the NICU. This may especially be the case if they receive conflicting information about infant readiness, breastfeeding techniques, and use of lactation aids, which are often required for NICU infants due to prematurity or medical/surgical conditions [27], [169].

16.5.1 Maternal Goals and Expectations

Although generally assumed, it is not necessarily the case that a NICU mother who pumps HM wants to feed at breast. A National Institute of Health-funded prospective cohort study of 352 VLBW infants showed that during early NICU hospitalisation (first 14 days post birth) the majority of mothers stated that their goal for HM feedings at discharge was either exclusive (62.9%) or partial (33.9%) HM, with only 3.2% electing to use exclusive formula [163]. However, of those mothers who wanted their infants to receive HM, only 10.6% wanted to feed exclusively at the breast and 8.3% wanted to feed exclusively pumped HM (e.g., no feeding at breast). The remaining mothers (81.2%) indicated that they wanted to feed HM through a combination of breast and bottle during the NICU hospitalisation and post-discharge period [163]. These data underscore the importance of tailoring protocols and messages to individual mothers’ goals for feeding at the breast rather than implementing a general approach. Similarly, some NICU infants are unable to consume oral feedings safely due to congenital anomalies, surgical conditions, and/or chronic sequelae of prematurity [169], [311], [312]. Every attempt should be made for HM feedings away from the breast to be as special as feedings at breast for NICU families. Previous studies have shown that NICU mothers derive great pleasure seeing their infants enjoy, thrive, and gain weight on their HM, regardless of how it is fed [162], [171], [200], [201], [311]– [314].

16.5.2 Developmentally-Based Breastfeeding Processes

Developmentally-based approaches to feeding premature infants at the breast in the NICU have been previously reviewed [27], [200], [315]–[319]; their major principles are summarised below. Nearly all experts propose a pathway that starts with skin-to-skin care for the smallest, sickest infants [27], [172], [320]–[322]. Multiple studies have demonstrated that the first developmental stage – skin-to-skin care – has many physiologic advantages for premature infants and their mothers and should be standard of care in NICUs worldwide [323]. There is evidence to suggest that during skin-to-skin care the infant transfers NICU microbes to the mother’s skin and respiratory surfaces, after which antibodies to these organisms are produced by the mother via the entero-mammary pathway [18], [324]. During this developmental stage, mothers should be encouraged to hold and/or touch infants while using the breast pump. Similarly, mothers should introduce oropharyngeal care with colostrum as soon as drops are available [27], [42], [248], [249].

Tasting HM at the breast

As soon as premature infants are extubated, nonnutritive feeds at the breast (referred to as tasting rather than drinking HM) can be initiated. Studies have demonstrated that non-nutritive sucking and/or low milk flow rates do not interrupt the swallow-breath process because ingested volumes are miniscule [325]–[329]. This key principle can be effected by the mother emptying her breast by pumping and then placing the small infant (including those with continuous positive airway pressure or high-flow oxygen) to the breast to taste HM (▶Fig. 16.4). A drop of HM can be expressed onto the nipple, allowing the infant to taste the HM and suckle non-nutritively. Ideally, these early breastfeedings coincide with the infant’s intermittent gavage feeding so that tasting and suckling occur while feedings are being received [318]. While there is no evidence that infants learn to breastfeed with these early feedings, mothers learn to position and provide head and neck support for the infant, as well as techniques for expressing HM drops onto the breast [27], [318], [319].

▶Fig. 16.4

The mother has used a breast pump to remove most of her human milk (HM) and then the infant is placed at breast to “taste” HM just prior to and during the gavage feeding. (® Rush Mothers’ Milk Club, 2016. All rights reserved)

Transition to nutritive feeds at the breast

Nutritive feeding progresses with the mother gradually pumping less HM before infant feeding, enabling the infant to master coordination of swallowing and breathing [27], [318], [319]. Several studies demonstrated greater physiologic stability during breastfeeding than during bottle feeding for premature infants who served as their own controls for the two feeding methods [306]– [308], [330]. There is neither evidence to support policies that require infants to effectively bottle feed before introducing breastfeeding, nor that gestational age alone predicts ability to feed at breast safely [27], [318], [319]. Once initiated, NICU care providers often limit the frequency/duration of individual breastfeeds due to concerns regarding fatigue and the negative impact on growth. There is no supportive evidence for this concern, particularly since infants’ physiologic stability is continuously monitored in NICUs. Of importance is the implementation of a modified cue-based feeding schedule as premature infants transition from gavage to breast, with bottle feedings introduced after the establishment of at-breast feedings [27], [172], [316], [331]–[333].

Measurement of HM intake during breastfeeding

As infants make the transition to cue-based breastfeedings, it is often important to know the volume of HM ingested during breastfeeding so that infant fluid balance and growth is maintained. Measurement of HM intake during breastfeeding can be made by test-weighing, whereby the clothed infant is weighed on a reliable electronic scale before and after the breastfeeding in exactly the same clothing and conditions [309], [310], [334]–[336]. The test-weighing procedure is extremely accurate when correctly performed by either NICU nurses or mothers [309], [310], [334], [335]. Although it is often assumed that clinical indices and assessment tools can replace test weighing, these other instruments are not accurate indicators of HM intake [309], [334], [337]. This means that while mothers and lactation experts may observe a breastfeed and score it the same way using an assessment tool, the score has no relationship to actual HM intake [309], [334], [337]. A simple clinical rule to follow is: if the volume of HM intake is not important to infant management at that time, do not test weigh; if it is important, perform test weights and do not rely on inaccurate scoring methods that are not evidence based.

16.5.3 Physiologic Immaturity

Premature infants remain physiologically stable during feedings at the breast but may consume an inadequate quantity of HM when breastfeeding exclusively, even when the mother can remove sufficient HM with a breast pump [180], [223], [224], [309], [314], [334], [338]. In a randomised clinical trial, mothers performed in-home measurement of HM intake for the first month post-NICU discharge using accurate test-weighing techniques [180]. All mothers had an adequate daily HM volume for their infants at the time of NICU discharge and intended to breastfeed exclusively, but infants could not consume all of the HM available to them (▶Fig. 16.5). Instead, the mothers needed to pump the extra HM each day and feed it by bottle to the infants. Each subsequent week at home post-NICU discharge, infants consumed increasingly larger volumes of HM from the breast, gradually breastfeeding exclusively at an average of 42 weeks PMA. This observation suggests that infant maturation rather than lack of practice and learning to feed at breast is the most likely reason for the infant’s inability to remove available HM effectively and efficiently during round-the-clock exclusive breastfeeds [27], [180].

▶Fig. 16.5

Mean daily intake of HM (human milk) by breast and bottle for 24 premature infants discharged from the NICU (neonatal intensive care unit) at a mean of 36±2 weeks PMA (postmenstrual age). This graphic illustrates that while infants have access to an adequate volume of HM each day, they are not able to remove it from the breast effectively until achieving approximately 40–44 weeks PMA. (® Rush Mothers’ Milk Club, 2016. All rights reserved)

Under consumption of HM feedings at the breast until 40–44 weeks PMA is primarily due to the fact that mature suction pressures (essential to creating and sustaining the nipple shape and to transferring HM) develop more slowly than expression pressures [27], [179]. Immature suction pressures manifest in infants’ slipping off the breast and requiring repositioning repeatedly during a feeding. Neurobehavioural immaturity exacerbates the weak suction because those infants who are still preterm on NICU discharge fall asleep early in the feeding after consuming minimal and insufficient amounts of HM [319]. In contrast, entire bottle feedings using standard commercial nipple units can be consumed by expression alone; thus, many premature infants consume more milk when bottle fed than during breastfeeding [327]. Many premature infants therefore need a bridge between NICU discharge and achieving the physiologic maturity to feed exclusively at the breast. This may be several weeks, especially in countries that prioritise early NICU discharge [27], [180]. Breastfeeding positions that provide support to the infant’s head, neck, and torso (▶Fig. 16.6), the use of thin silicone nipple shields (▶Fig. 16.7) and use of test weights are examples of these temporary breastfeeding aids [309], [310], [334], [335], [339], [340].

▶Fig. 16.6

Use of breastfeeding positions that support the infant’s head and neck can help to compensate for weak intraoral suction pressures. (® Rush Mothers’ Milk Club, 2016. All rights reserved)

▶Fig. 16.7

Use of ultrathin nipple shields can help to compensate for weak intraoral suction pressures, thus facilitating HM intake during breastfeeding in premature infants. (® Rush Mothers’ Milk Club, 2016. All rights re- served)

Ineffective and inefficient HM removal during breastfeeding can also compromise the regulation of lactation. Many mothers will need to continue to breast pump to protect HM volume until their infants are exclusively feeding at breast [179]. For example, the infants in ▶Fig. 16.5 were able to progress to consuming an adequate HM volume and eventually breastfeed exclusively because the hospital-grade electric breast pump provided effective and efficient mammary gland stimulation during the weeks when infants were unable to do this independently [27], [180].

The evidence that links physiologic immaturity to effective and efficient HM removal during feedings at the breast conflicts with many of the common practices and interventions for healthy term infants and mothers. An overriding principle of planning post-NICU breastfeeding care (e.g., breastfeeding management at home) with families is to consider the premature NICU infant as not just a small healthy term baby. Families must understand that the inability of the premature infant to extract HM effectively and efficiently is not solved by NICU discharge alone (e.g., lack of physical infant-mother separation). This misunderstanding is most apparent in instructions to feed on demand and everything will be fine. Information in ▶Table 16.3 can be used to prepare families for the misleading and potentially unsafe advice they can receive from family, friends, and health care providers that work with healthy breastfeeding infants. ▶Fig. 16.5 may help families to comprehend the gradual increase in HM intake with each successive week post-NICU discharge; clinicians should emphasise that each infant is different with some making this transition sooner than others. Plans to supplement feedings at breast with pumped HM in the home until exclusive breastfeeding is achieved have been previously reported [27].

▶Tab. 16.3 Common recommendations about post-NICU breastfeeding that are inappropriate and appropriate for premature infants.


Common Recommend-ations

Inappropriate because

Correct Recommend-ation

  • Infant falls asleep early in the breastfeeding with little or no effective sucking and/or HM removal

  • “The baby is too comfortable”

  • “Unwrap the baby to help him stay awake”

  • “Just let him sleep. He will wake up and feed when he is hungry”

  • Sleepiness is normal, not abnormal, for a premature infant. Breastfeeding must be adapted to fit the sleepiness

  • Premature infants are at risk for hypothermia when subjected to cold stress

  • Decreased adipose stores deplete quickly with increase metabolic rate, and can compromise adequate weight gain

  • Start feeding immediately when infant awakens. Do not change diaper or wait for infant to become “more awake”

  • Reassure parents that this behaviour is normal, and that some bottle supplementation with pumped HM may be necessary temporarily

  • Baby slips off the nipple easily and/or frequently, despite achieving an effective initial latch

  • Feedings are inefficient, taking up to 1 hour with little HM transfer

  • However, baby feeds from bottle quickly and consumes large volumes

  • “The baby is just ‘lazy’ and has gotten used to a bottle-feeding nipple”

  • “The baby just does not want to ‘work’ at breastfeeding”

  • “Infant does not need as much milk as she consumes from the bottle”

  • “This is ‘nipple confusion’ and the infant should receive complementary cup or other alternative feeds of expressed HM”

  • This is normal feeding behaviour through 40–44 weeks PMA

  • Strong infant suction pressure is necessary for breastfeeding, and is maturationally dependent

  • Bottle feeds do not require mature suction pressures, so babies can drink larger volumes more quickly

  • This is not “laziness” or “not wanting to work” at breastfeeding

  • Use positions that support the infant’s head, neck and torso

  • Consider the use of a nipple shield if positioning alone does not correct the problem of slipping off the nipple

  • Do not have mothers “triple feed” during this time due to exhaustion. Set aside breastfeeding times and bottle feed/ pumping times to protect HM volume and infant intake

  • Not knowing if the infant is consuming an adequate volume of HM during breastfeedings

  • “Every mother worries if her baby is drinking enough milk. So, just feed on demand and everything will be OK”

  • “You are pumping enough milk, so you know your baby is getting enough milk”

  • “You just got addicted to the numbers in the NICU”

  • “You can count wet diapers, bowel movements, and note if your breasts feel empty after feeding”

  • Premature babies are at risk for not getting enough HM during exclusive breastfeeding, so mothers should not be reassured as if the babies were healthy and full term

  • Pumping enough HM does not mean that the baby can remove the same amount of HM as the pump

  • Numbers are important in the NICU and the early post-discharge period because the difference between enough HM and not enough HM is much smaller for a premature baby

  • These common indicators (wet diapers and bowel movements) are not sufficiently sensitive to detect adequacy of intake in premature babies

  • Reassure the family that these are universal concerns when breastfeeding a premature baby after NICU discharge

  • Implement test-weighing procedures in the NICU to measure HM intake during breastfeeding so mothers acquire beginning ability to match feeding behaviours with infant intake

  • Continue the use of test-weighing post-NICU discharge if desired by the mother in order to achieve her personal HM feeding goal

  • Suspecting that the infant consumes small volumes during a breastfeeding

  • “Your baby is probably just a ‘snacker’. Lots of babies are like this”

  • “Just feed more frequently so that your baby gets enough milk over the day”

  • “Wake your baby every hour or two if necessary to feed her”

  • Studies reveal that these mothers are usually right, and babies do consume small amounts per feeding

  • It is unsafe to wake a premature infant so frequently due to interrupted sleep and resultant fatigue and slow growth

  • The breastfeeding plan should be adapted to facilitate sleep, not vice versa

  • Supplement at-breast feedings with pumped HM to ensure that infant “gets enough” until infants are able to feed at breast effectively and efficiently

  • Use ▶Fig. 16.5 to illustrate this concept for families

  • Overwhelming desire to discontinue pumping, nipple shield, test weights, etc., and feed exclusively from the breast

  • “You are home with your baby now so you do not need all of that ‘stuff’. Just feed your baby on demand”

  • “Look at all that milk you get when you pump. You know that’s enough for your baby”

  • “You want to get your baby off the nipple shield as soon as you can because it will interfere with your milk supply”

  • Early discontinuation of lactation aids compromises both infant intake and maternal HM volume until infant feeds effectively and efficiently at breast

  • Ability to remove HM by the breast pump does not translate into infant’s ability to remove it via breastfeeding

  • Discontinuation of the nipple shield prior to maturation of suction pressures places the infant at risk for consuming insufficient HM volumes

  • Raise this matter with families before NICU discharge so they are prepared for this wrongful advice when they return to the community

  • Use Figure 5 to demonstrate how continued breast pump use created the HM that the infant would not have been capable of by breastfeeding alone, enabling exclusive breastfeeding later post-NICU discharge

  • Emphasise that if the infant consumes more HM with than without the nipple shield, it should not be discontinued

HM = human milk, NICU = neonatal intensive care unit, PMA = postmenstrual age. ® Rush Mothers’ Milk Club, 2016

16.5.4 Summary – Feeding at Breast

Developmentally-based at-breast feeding focuses on a trajectory of events that includes skin-to-skin care, pumping HM at the infant’s bedside; tasting HM at the breast, and nutritive feeding of HM. Maternal breastfeeding goals are highly individual, and may include exclusive HM feeds at breast, exclusive HM feeds via bottle, or a combination of the two methods. Ascertainment of these goals is a critical component of NICU lactation care. While preterm infants remain physiologically stable during at-breast feeding, they typically consume less HM volume than is required for hydration and growth until approximately 40–44 weeks PMA. During the period between NICU discharge and achievement of full at-breast feedings, lactation aids such as test weighing, nipple shields, at-home pumping, and bottle (or alternative) feedings are frequently necessary so that mothers can achieve their individual HM feeding goals.

16.6 Overall Summary

For the premature infant, HM represents a safe, cost-effective strategy for reducing the risk of many morbidities and their associated costs during and after NICU hospitalisation. This protection is related to HM dose. It is provided by the multiple HM components that function synergistically to selectively grow and protect developing body organs from NICU stressors including inflammation, oxidative stress, and improper/inadequate nutrition. Donor HM does not provide the same protection as HM for reasons that extend beyond pasteurisation. Despite this knowledge, NICU mothers struggle to achieve their personal HM feeding goals and their infants receive a lower lifetime HM dose as a result of inadequate HM volume.

Mothers do not routinely receive state-of-the-art lactation care provided by NICU specialists with expertise in managing breast pump-dependency, coming to volume strategies, HM compositional analyses and modification, test weights, nipple shields, and other lactation aides. Substantial evidence exists to standardise best practices for the care and feeding of HM in the NICU, but individual provider preferences and cost concerns frequently take priority. Specifically, evidence supports the feeding of fresh (e.g., never frozen, never pasteurised) HM, prioritising early feeding of colostrum over mature HM, and storing all pumped HM in commercial refrigerators and freezers in the NICU. HM routine culturing and pasteurisation, and use of water baths to thaw and/or warm HM should be avoided. Developmentally-based approaches to at-breast feeding include skin-to-skin care, pumping at the NICU infant’s bedside, tasting HM, and feeding nutritively at the breast. Evidence worldwide suggests that premature infants are vulnerable to consuming inadequate volumes of HM directly from the breast until approximately 40–44 weeks PMA. The overarching priority for optimising HM feeding in the NICU is to implement standardised protocols and best practices that translate the evidence into NICU practice.

Key Points

  • Human milk from the infant’s own mother should be the feeding method of choice for all infants in the neonatal intensive care unit with the aim to administer fresh mothers own milk and frozen milk as the next best option

  • Human Milk from the infant’s own mother has been found to reduce the risk and/or severity of multiple serious, potentially handicapping and costly morbidities in premature infants

  • Protection by human milk is provided via its many components, which function synergistically to selectively grow and protect developing body organs. This protection has been found to be directly proportional to the quantity of milk received

  • Standardised protocols and best practices are required to support mothers of pre-terms infants to achieve their personal human milk feeding goals

Professor Paula P. Meier, PhD, RN, FAAN, Professor of Paediatrics and of Women, Children and Family Nursing, is the Rush University, Chicago, Neonatal Intensive Care Unit Human Milk Research Team director and lead human milk scientist. This clinically-based multidisciplinary team’s overarching goal is removal of barriers to high-dose human milk feeding for infants in the neonatal intensive care unit. Formed in 2000, this team has conducted a diverse range of research studies, such as on the preterm infant gut microbiome, counselling breastfeeding mothers, and adapting diagnostic tools to better manage human milk feeding strategies.


This work was funded by two NIH grants: NIH R010009 (Meier PI) and NIH R03HD081412 (Patel PI).


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