KEY POINTS
- 1.
The benefits of enteral nutrition for the preterm infant extend beyond growth and encompass gastrointestinal development and gut inflammatory balance.
- 2.
Preterm infant intake of mother’s milk, including oral immune therapy, is associated with improved outcomes.
- 3.
Pasteurized donor human milk is the preferred feeding supplement when mother’s milk is contraindicated or unavailable and is associated with less necrotizing enterocolitis compared with formula.
- 4.
Preterm infants tolerate initiation of enteral nutrition as early as the first postnatal day and most tolerate advancement of 30 mL/kg/day with no difference in long-term outcomes compared with infants with slower feed advancement.
- 5.
Fortification of human milk with a multinutrient human milk fortifier is necessary to meet energy, protein, mineral, and micronutrient requirements and support growth.
- 6.
Standardized fortification may not meet the needs of all infants due to variations in human milk composition. Modification of feeds should be individualized to support growth, especially for infants with higher energy and protein demands.
- 7.
Exact protein needs are not well-defined; however, maintaining a protein intake of 3.5 to 4.3 g/kg/day with a minimum of 110 kcal/kg/day is recommended.
- 8.
Sustaining mother’s milk feeding with nutrient supplementation as needed to sustain adequate growth appears to be the best enteral nutrition practice to optimize neurodevelopment.
- 9.
More research is needed to define the optimal diet of the very low birth weight infant at hospital discharge; however, supplementation of human milk with a multinutrient human milk fortifier for ≥50% of feedings until 52 weeks’ postmenstrual age should be considered.
Introduction
Enteral nutrition delivery to preterm infants is evolving. Product options in preterm formula and human milk fortifier, availability of donor human milk, and improved methods to support maternal milk production have increased greatly in the past decade. Furthermore, the recognition that human milk feeding protects against necrotizing enterocolitis (NEC) has transformed the approach to preterm infant feeding from a belief that the infant must show that he is “safe” to be fed to a concept that feeding is protective, and therefore, initiation and continuation of feeding should be prioritized. Yet work is still needed in the design of methods to optimize nutrient delivery, including ways to minimize nutritional loss in human milk from the time of collection until the time the infant receives the feed. Furthermore, methods to protect preterm infants by extending the duration of mother’s milk feeds, ensuring safe donor milk options, developing reliable probiotic options, and identifying the best enteral nutritional intake to optimize neurodevelopment should all be prioritized.
Preterm Infant Gastrointestinal Tract
When an infant is born preterm, the gastrointestinal tract must continue to develop outside the intrauterine environment, and while developing, it also must function to both absorb nutrients and block pathogens. At birth, the preterm infant gut is no longer exposed to amniotic fluid, which delivers 15% of fetal nutrition and provides growth-stimulating cytokines to the developing intestinal wall. Fortunately for the preterm infant, human milk and amniotic fluid share a cytokine profile that fosters maturation of the intestinal wall and immune system , ( Table 19.1 ). Unlike the fetus who has minimal if any intestinal microbes, development of the preterm infant gastrointestinal system includes microbial colonization ( Fig. 19.1 ). NEC occurs when the infant’s intestinal barrier, antiinflammatory mediators, and commensal bacteria incline toward a proinflammatory process.
| In fetal intestine, amniotic fluid, and human milk |
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| In amniotic fluid and human milk |
|
For the intestinal barrier, intestinal permeability is a marker of gut immaturity and is measured by the leakiness of the tight junctions between intestinal epithelial cells. Intestinal permeability is high at birth and is much higher in preterm infants compared with full-term infants. Intestinal permeability decreases with postnatal age and decreases with intake of mother’s milk in both full-term and preterm infants. Intestinal permeability appears to be associated positively with intestinal microbial diversity, and one study demonstrated decreased permeability with a bifidobacterium supplement to cow’s milk for preterm infants. ,
Therefore, beyond providing adequate nutrition to achieve growth, gastrointestinal development and gut inflammatory balance are critical considerations in regard to enteral nutrition for a preterm infant. The type of feeding, timing of feed initiation, and speed of feed advancement not only are factors important for nutrient delivery but also have been studied extensively for their role in gut health. Additionally, consistency and accuracy in diagnosis of gut health and feeding tolerance is critical in safe enteral nutrition delivery. Refer to Fig. 19.2 for other nutritional limitations in the premature gastrointestinal tract.
Human Milk Production and Delivery
Preterm infant health outcomes are optimized with intake of human milk. Unfortunately, efforts to ensure mothers can initiate and sustain lactation are not adequate for all mothers. Methods that have been shown to be beneficial are provided in Table 19.2 . Human milk feedings of mother’s milk supplemented as needed with donor human milk are associated with significantly less NEC, less sepsis, and less severe retinopathy of prematurity. Benefit is seen in lower NEC and sepsis rates with exclusive human milk versus exclusive preterm formula, any human milk versus exclusive preterm formula, and higher versus lower human milk doses. For sepsis, the dose-dependent effect is observed in observational studies but not randomized-controlled trials. Meta-analysis also shows a potential decrease in severe retinopathy of prematurity. Evidence of a decrease in bronchopulmonary dysplasia is less certain. Mechanisms by which human milk protects the infant from disease are shown in Fig. 19.3 .
| To Sustain Mother’s Milk to 40 Weeks’ Postmenstrual Age | To Have Adequate Milk Supply at Hospital Discharge |
|---|---|
| Express milk by 6 hours postbirth Perform kangaroo care Express milk at least 5 times per day | Pump both breasts simultaneously Produce 500 mL/day milk by postnatal day 10 Describe breast pumping as comfortable Have a NICU environment with:
|
Early Enteral Nutrition
Oral Immune Therapy With Mother’s Milk
Oral immune therapy, or oral colostrum care, is when milk is placed on the infant’s buccal mucosa. A Cochrane Review of six studies including 335 infants concluded that days to full enteral feeds were reduced, with a mean difference of −2.58 days (95% confidence interval [CI], −4.01 to −1.14) in the group that received oral colostrum care. Evidence of potential immune benefit also has been demonstrated, with increased urinary lactoferrin and immunoglobulin A concentrations with oral immune therapy versus placebo. Of note, the benefits of oral immune therapy are more apparent when the milk is delivered with a syringe versus a swab.
Initiation of Feeds
Unless there is abdominal pathology or cardiovascular compromise, feeds should be initiated as early as the first postnatal hours and as late as 3 days. Meta-analysis results show no benefit to delaying feeds to 4 days or longer, including no decreased risk of NEC. Even though the meta-analysis demonstrates no benefit to introduction of feeds before 4 days, if early introduction leads to earlier attainment of full enteral nutrition, then central-line days and parenteral-nutrition days may be decreased, leading to less risk for infection, complications, and cost. As to how early is too early to initiate feeds, no study has demonstrated an early time that is associated with morbidity. In a trial by the Abnormal Doppler Enteral Prescription Trial Collaborative Group that included infants born at less than 35 weeks with intrauterine growth restriction, outcomes were no different with initiation of feeds by 48 hours compared with after 48 hours in the whole group and in the subgroup of infants born at less than 29 weeks’ postmenstrual age (PMA). In regard to potential benefit with earlier feeding, intestinal permeability is highest when an infant gut is not fed. Additionally, one study showed increased inflammatory markers in stool and increased inflammatory diseases such as bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) with delaying feed initiation until after the third day. Another study demonstrated tolerance when extremely low birth weight infants were fed at a median of 14 versus 33 hours and found less central-line-associated infections and less feeding intolerance and higher growth velocity in the cohort fed earlier. A potential evidence-based guideline for feed initiation is provided in Table 19.3 .
| Feeding Volume | Feeding Type | ||
|---|---|---|---|
| Days 1–3 | Initiate feeds 12–25 mL/kg/day a | <1500 g or <32 Weeks | >1500 g and >32 Weeks |
| Mother’s milk supplemented with donor human milk | Mother’s milk supplemented with preterm formula | ||
| Days 2–4 | Initiate feed advancement by 25 mL/kg/day | ||
| Days 3–12 | Increase feed volume by 25 mL/kg/day to full volume, 120–160 mL/kg/day | Fortify with high-protein bovine-derived fortifier or human milk–derived fortifier at least at 100 mL/kg/day or as early as the first feed | Fortify with standard protein bovine-derived fortifier at least at 100 mL/kg/day or as early as the first feed; if formula feeding, start with 24 kcal/oz formula at first feed |
| Discharge | No less than 120 mL/kg/day when taking volumes ad libitum | If human milk–fed: Fortify with standard protein bovine-derived fortifier for ≥50% of feedings for up to 52 weeks’ postmenstrual age If formula fed: Preterm-discharge formula until minimum of 40 weeks’ corrected age; preterm formulas may be considered in some circumstances, i.e., severe growth restriction, metabolic bone disease | Provide preterm-discharge formula or supplement mother’s milk with preterm-discharge formula until at least 40 weeks’ corrected age |
| Transition infants to either unfortified human milk/breastfeeding or to standard formula (for formula-fed infants) once the infant regains his or her birth percentile | |||
a Full-term breastfed infants: feed 10–15 mL/feed on day 1, 15–20 mL/feed on day 2, 20–25 mL/feed on day 3, and 25–30 mL/feed on day 4. Consider limiting to these volumes even in infants who weigh >3 kg.
Enteral Feeding Selection
Human Milk
Human milk is the preferred feeding for nearly all infants, with numerous short and long-term advantages to the very low birth weight infant. There are few contraindications to feeding mother’s own milk ( Table 19.4 ). The use of marijuana during breastfeeding is one subject of debate, especially because lipid-rich milk is the ideal vector for cannabinoid metabolites. Unfortunately, long-term consequences due to exposure to human milk cannabinoids are not well described, and studies are confounded by use of other recreational substances like tobacco and alcohol. The American Academy of Pediatrics (AAP) highlighted concern for neurodevelopment and growth sequelae with marijuana use during both pregnancy and lactation in a recently published report. However, due to the lack of evidence, the guideline does not state that lactation is contraindicated for a mother who is using marijuana. Consequently, with the currently available information, mothers who are using marijuana should be educated regarding the potential consequences to their infant’s growth and neurodevelopment and given appropriate social support and counseling, but after education, if the mother continues to provide her milk, she should be supported in her lactation.
| When to substitute formula or donor milk for mother’s milk |
|
| When to temporarily substitute formula or donor milk for mother’s milk |
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| When to not feed directly from the breast (but feeding mother’s milk from bottle is acceptable) |
|
| When to only feed formula (no human milk) |
|
| HTLV, Human T-lymphotropic virus. |
For most medications, the benefits of mother’s milk for a preterm infant likely outweigh the potential harm of the medication. However, for some medications with minimal research, it is important to obtain the available drug information and discuss the risk benefits to develop a consensus among the interdisciplinary clinical care team and the family. Available resources are provided in Table 19.5 .
| Resource |
| LactMed https://www.ncbi.nlm.nih.gov/books/NBK501922/ |
| Mother to Baby (a service of the nonprofit Organization of Teratology Information Specialists) https://mothertobaby.org/ |
| InfantRisk Center (a service of Texas Tech University Health Sciences Center) http://www.infantrisk.com/categories/breastfeeding |
| CDC Breastfeeding and Special Circumstances: Vaccinations, Medications, & Drugs https://www.cdc.gov/breastfeeding/breastfeeding-special-circumstances/vaccinations-medications-drugs/prescription-medication-use.html |
| University of Rochester Medicine Breastfeeding Provider Resource Telephone Consultations for Healthcare Providers https://www.urmc.rochester.edu/breastfeeding/provider-resources.aspx |
It is important to note that the processes of pumping, storage, freezing, thawing, and preparing human milk feeds for neonatal intensive care unit (NICU) infants decrease concentrations of some nutritional and immunologic components of mother’s milk. When providing mother’s milk via tube, fat, vitamin C, vitamin B 6 , carotenoids, calcium, and phosphorus are at risk for loss during tube feedings. Therefore, attention to providing the freshest mother’s milk in the shortest time benefits nutrition and immune-component delivery to the NICU infant.
Donor Human Milk
When mother’s milk is not available, donor human milk is a feeding type associated with less NEC compared with formula feeding. Current sources of donor human milk include raw milk, pasteurized milk (Holder or vat), and retort-sterilized milk. In a recent meta-analysis of 12 trials of donor human milk and preterm formula, all studies used pasteurized (Holder or vat) donor human milk except for one that used raw milk. No studies in this meta-analysis used retort-sterilized human milk. Three trials added bovine-derived milk fortifier to the donor milk, and one added human milk–derived milk fortifier. The meta-analysis results demonstrate significantly better weight, length, and head growth with formula compared with donor human milk. No difference in neurodevelopment was observed between infants fed formula or donor human milk. Formula-fed infants had a significantly higher risk of NEC (relative risk, 1.87; 95% CI, 1.23–2.85) with a number needed to treat of 33 preterm infants with donor milk to avoid one case of NEC. The trials of donor human milk versus formula differ in their populations and duration of treatment, but many institutions and even state quality-improvement initiatives have chosen to provide donor human milk to the infants most at risk for NEC during the time that they are most at risk. A common standard is to provide donor human milk as a supplement to mother’s milk for all hospitalized very low birth weight (<1500 g) and very preterm (<32 weeks’ PMA) infants until they reach 34 weeks’ PMA.
Although the benefit of donor human milk to prevent NEC is critical to preterm infant care, all donor human milk is lacking in some nutritional and immunologic factors compared with mother’s milk. The lower values in donor human milk are due to differences in milk expressed for a preterm versus a full-term infant, the loss of nutritional and immunologic function with pasteurization or retort processing, and the loss of nutritional and immunologic concentrations during freezing, thawing, and container transfers that occur in donor milk processing. Preterm milk is higher in protein, sodium, and immune components (beta-defensin, secretory CD14 receptor, transforming growth factor–β 2, and potentially lysozyme) than is term milk. In the pasteurization process for donor milk, live cells are killed and enzymes (such as lysozyme, alkaline phosphatase, amylase, and lipase) are inactivated. Additionally, immunoglobulins and water-soluble vitamins are reduced in the pasteurization process.
Pathogen-free donor milk is available from nonprofit and for-profit milk banks with milk processed by Holder pasteurization, vat pasteurization, and retort processing for a shelf-stable milk. Other processes being investigated as methods to provide safe donor milk include high-pressure processing, high-temperature short-time pasteurization, UV irradiation, and (thermo-) ultrasonic processing. Table 19.6 compares sources of human milk and implications on processing methods. ,
| Products (Distributors) | Processing Type and Description | Effects on Processing | Additional Information |
|---|---|---|---|
| MOM | Fresh milk preferred because changes to composition are observed with freezing | Freezing MOM ↓ concentration of lysozyme, secretory IgA, and lactoperoxidase Calorie and fat content decreases with freezing time; significant differences are observed at 90 days | Maximum recommendations for safe hold times: https://www.cdc.gov/breastfeeding/recommendations/handling_breastmilk.htm Average composition of human colostrum and mature breastmilk are available |
| Pasteurized donor milk (Human Milk Banking Association of North America—includes the United States and Canada) https://www.hmbana.org/ | Holder Pasteurization Initial freeze/thaw cycle, heated to 62.5°C during pasteurization process, then rapidly cooled to 4°C and stored frozen at −20°C or less Distributed to units frozen and must be thawed prior to being fed to infant Average of 2–6 mothers per batch | Eliminates bile salt–stimulated lipase ↓ Lactoferrin, IgA, IgM concentrations compared with MOM ↓ Lysozyme and secretory IgA activity compared with MOM, although retains significantly higher activity compared with retort sterilization | Must remain frozen and used within 48 hours of thawing/refrigeration Mothers are screened for health and drug/tobacco use and blood tested for bloodborne pathogens Mothers are not compensated for donation Milk is prioritized to preterm infants Labeling of calories and protein specific to individual milk banks and nutritional analysis may be used to target pool milk to obtain a minimum of 20 calories per ounce |
| PremieLact Prolact HM (Prolacta Bioscience) https://www.prolacta.com/ | Vat Pasteurization Similar to Holder Pasteurization with two freeze/thaw cycles Milk is heated to 63°C for ≥30 minutes; additional details are proprietary Average of 250 mothers per batch | Fat and energy concentration significantly higher compared with the retort sterilization although not different compared with Holder Pasteurization | Must remain frozen and used within 48 hours of thawing/refrigeration Mothers are compensated for donation Donors are blood tested for bloodborne pathogens, and donated milk undergoes nucleic acids amplification testing for pathogenic viruses and bacteria Donor milk is DNA matched to the donor Donor milk is tested for microbes, adulteration, nicotine, and drugs of abuse Uniform caloric density with nutrition content provided on the product label; nutritional analysis via wet chemistry tests Guarantees a minimum of 20 calories/ounce and provides an average of 1.1 g protein per 100 mL |
| BENEFIT-18 BENEFIT-20 BENEFIT-24 (Medolac Laboratories, Boulder City, Nevada) https://www.medolac.com/ | Retort Sterilization Initial freeze/thaw cycle, milk heated to 121°C for 5 minutes under pressure of 15 pounds per square inch; distributed in shelf-stable packaging | ↓ Lysozyme and secretory IgA activity compared with MOM and Holder/Vat Pasteurization ↓ Protein, fat, immune-modulating proteins, and HMO function compared with Holder/Vat Pasteurization | Shelf-stable at room temperature for 3 years Commercially sterile and homogenized Can be refrigerated for 7 days after opening Mothers are compensated for donation Milk is tested for pathogens both before and after processing Uniform caloric density: Nutrition content provided and specific to each lot with minor variation between lots Refer to company-specific website for details; nutritional analysis via third-party analysis BENEFIT-24 is ultrafiltered and has increased amounts of key nutrients including 1.78 g protein per 100 mL and 24 calories/ounce |
| HDM Boost HDM Plus (Ni-Q) https://www.ni-q.com/ | Proprietary Agitating Retort Process | No information available | Shelf-stable at room temperature for 12 months Commercially sterile and homogenized Donors are blood tested for bloodborne pathogens Donor milk is screened for alcohol and microbial contamination and is genetically tested to ensure donor matching Mothers are compensated for donation Uniform caloric density: nutrition content provided and specific to each lot, with minor variation between lots Refer to company specific website for details; nutritional analysis validated by a third party Calorically enhanced using a patent pending system: HDM Boost has a minimum of 1.5 g protein and per 100 mL and 24 calories/ounce HDM Plus has a minimum of 20 calories/ounce |
| Informally shared milk (includes any milk other than mother’s own, i.e., milk from either the Internet or a known source) | None | No information available | Risks poor handling and inadequate temperature holding; thus no guarantee that milk is safe from harmful bacteria May be diluted with bovine milk or other nonhuman milk source No blood testing performed for transferrable diseases |
Mothers should be educated on the dangers of informal milk sharing. One group of investigators obtained and analyzed more than 100 samples of human milk from the Internet. The majority of samples were found to have evidence of dilution with bovine milk, high counts of bacterial growth, and evidence of mothers’ use of nicotine and caffeine. Poor handling, storage, and shipping techniques were described. Although fresh mother’s milk that has never been frozen is the preferred source of feeding for the preterm infant, it is possible for human milk to have a bacterial or viral load that may be injurious to the infant. , One example is a mother with reactivated cytomegalovirus. Shedding of the virus can be detected in colostrum as early as 3 days. However, even though a preterm infant may become infected from cytomegalovirus in maternal milk, the benefit of fresh maternal milk appears to outweigh the risk of viral infection. The same cannot be said for informally shared donor milk. Therefore, shared donor milk even from a “trusted” source should not be provided to a hospitalized preterm infant. Institutions should have a policy that prohibits or at least requires parental informed consent for use of raw milk other than the mother’s own, especially for the high-risk, immunocompromised infant.
Despite great efforts to obtain mother’s milk as early as possible, when a mother is not directly breastfeeding, the ability to obtain milk drops via pump or hand expression may be difficult, especially in the early days. Therefore, a common question in preterm infant care is whether feeds should be started with donor human milk or formula or whether feed initiation should be delayed until mother’s milk is available. The second question, then, is how long is it appropriate to wait for mother’s milk? Unfortunately, evidence to answer these questions is lacking. Due to the apparent low toxicity of donor human milk, many institutions initiate donor human milk while awaiting mother’s milk. When an infant does not “qualify” to receive donor human milk, and therefore, formula would be the initial feeding type, the practice is quite varied even within an institution. Until studies are performed to address these questions, no evidence-based recommendation is available. For the very low birth weight infant or very preterm infant, if a supplement to mother’s milk is needed, donor human milk is the current standard of care until the infant is out of the PMA at which NEC risk is greatest. A common practice is to provide donor human milk to all infants born weighing <1500 g and/or at <32 weeks’ PMA until they reach 34 weeks’ PMA or until hospital discharge (whichever occurs first), but variations on this practice are widespread. Based on a Cochrane Review meta-analysis, the evidence-based goal with donor human milk is to provide it to preterm infants to decrease the risk of NEC. Therefore, providing it to the infants most at risk for NEC during the time that they are most at risk for NEC is an evidence-based practice. The donor human milk provided to very preterm infants should be pasteurized donor milk.
Preterm Infant Formula
For neonatal units without access to donor milk or for larger premature infants who do not meet specific weight or gestation criteria to receive donor milk, preterm formula is recommended when mother’s own milk is not available. Modest improvements of in-hospital growth are observed compared with standard formulas. Preterm formulas are higher in protein, calcium, and phosphorus, contain a fat source that is predominantly medium-chain triglyceride-based, and have lactose and glucose polymers as their carbohydrate source to enhance digestion of calcium. Ready-to-feed, 24-calories-per-ounce preterm formulas have an osmolality similar to that of breast milk (280–320 mOsm/kg water) and may be used from the start of the first feeding in the absence of human milk. Available preterm formulas are whey-predominant with varying amounts of protein, between 3.0 and 3.6 g per 100 calories. Higher-protein formulas may be best suited for the fluid-restricted infant in order to meet protein goals; however, providing >4 g/kg/day of protein long term in formula-fed infants has not been well-studied, and evidence is limited in terms of safety or neurodevelopmental outcomes. Additionally, there is inconclusive evidence that use of a hydrolyzed protein formula for “easier digestion” affects the risk of NEC. There are currently no protein hydrolysate or amino acid formulas within the US market that are designed to meet the nutritional requirements of preterm infants, and concern exists for nutrient bioavailability, especially with regard to protein, calcium, and phosphorus.
Advancement of Feeds
Preterm infants have small gastric size and slow motility; therefore the initial feeding volume is small, with the volume advanced over days. Historically, rapid advancement of feed volume appeared to be associated with a higher risk of NEC. However, most but not all contemporary studies have disproved that association. Recent retrospective cohort studies have demonstrated a decrease in NEC with a slower feed initiation and advancement practice, but randomized, controlled trials show no benefit. A 2014 Cochrane Review reported both no evidence of benefit for trophic or minimal volume feedings for a few days prior to feed advancement and no benefit to advancing less than 24 mL/kg/day. , The Speed of Increasing Milk Feeds Trial (SIFT) is a randomized, controlled trial of very low birth weight or very preterm infants randomized to receive feed volume advanced by 30 or 18 mL/kg/day increments. At 2 years of age, the two groups demonstrated no difference in outcomes including incidence of NEC and late-onset sepsis. Although no benefit was demonstrated with feed advancement of 30 mL/kg/day, no detriment was observed either. With the risks and costs of parenteral nutrition, including both the compounding and the vascular access and also the difficulty of providing adequate nutrition, especially with the ever-recurring shortages of nutrients, the current evidence points to 30 mL/kg/day as an acceptable and potentially beneficial feed volume advancement strategy. In fact, the available evidence led the authors of one meta-analysis to recommend achieving full enteral nutrition within 7 days for infants born weighing 1 to 1.5 kg and within 14 days for infants born weighing <1 kg, which is indeed feasible and has been established in clinical practice.
Nutrition Requirements
Protein
Early and adequate protein intake is key to preventing accumulation of protein deficits in the preterm infant. Although studies have not identified the ideal protein requirement of the preterm infant, achieving a slightly higher enteral protein intake compared with parenteral intake is recommended due to incomplete and immature digestion and the biologic value of enteral protein sources. Older guidelines for protein were created on the basis of fetal accretion rates during gestation and have been adjusted over time. Current available evidence points to protein goals in the premature infant ranging from 3.3 to 4.3 g/kg/day. In randomized, controlled trials, higher protein intakes of 3.3 to 4.3 g/kg/day versus 2.8 to 3.7 g/kg/day are significantly associated with improved weight, height, and head circumference growth, but not consistently. This lack of consistent efficacy may be due to an overlap in protein delivery, as demonstrated by three studies defining protein intake of 3.6 to 3.7 g/kg/day as low protein. Additionally, the studies were also complicated by variation in maternal protein content. One recent study did not show any growth benefit with higher protein fortification (3.7 g/kg/day vs. 4.3 g/kg/day) when milk protein content was confirmed with human milk analysis. This suggests a saturation point or ceiling-effect of protein on growth in the preterm infant. Variation of growth is more likely contributed to an energy deficit when protein needs are met.
Calories
Energy needs of the premature infant are estimated based on several factors in addition to basal energy expenditure and requirements for growth and lean body mass deposition. Factors that are unique to the individual infant include levels of physical activity, temperature support, thermic effect of food, losses of energy in stool and urine, and clinical condition/disease state, that is sepsis or chronic lung disease. Exact energy requirements are difficult to identify based on the influence of protein on growth and the varying protein energy ratios in empirical studies. One group of studies that specifically identified the protein-to-energy ratio instead of protein or energy quantities alone identified a caloric intake of approximately 115 kcal/kg/day with a protein intake of 3.6 g/kg/day needed to achieve weight gain of 16 to 22 g/kg/day. A greater supply of energy, upwards of 150 kcal/kg, produced more body fat measured by triceps skinfold; however increasing protein above 4 g/kg/day did not increase gains in lean body mass. Preterm infants do require a minimum of 110 kcal/kg/day to maintain fat deposition similar to the normally growing fetus. Adequate caloric intake is needed to maximize nitrogen retention with increase in protein delivery, as illustrated in Fig. 19.4 . Our recommendations for calories and protein are outlined in Table 19.7 . Enteral nutrient recommendations from different sources are compared in Table 19.8 .
| Age | Energy Goal (kcal/kg) | Protein Goal (g/kg) |
|---|---|---|
| Preterm <34 0/7 weeks | 110–130 | 3.3–4.3 a |
| Late preterm 34 0/7 to 36 6/7 weeks | 120–135 | 3–3.2 |
| Term ≥37 0/7 weeks | 105–120 | 2–2.5 |
a Authors recommend slightly less protein compared with original text given limited data for higher protein intakes above 4.3 g/kg/day. Adapted from Goldberg DL, Becker PJ, Brigham K, et al. Identifying malnutrition in preterm and neonatal populations: recommended indicators. J Acad Nutr Diet . 2018;118(9):1571–1582.
| Nutrient per kg | Koletzko, 2014 | ESPGHAN, 2010 | LSRO, 2002 (Formula-Fed Infants Only) |
|---|---|---|---|
| Energy, kcal | 110–130 | 110–130 | 100–141 |
| Protein, g | 3.5–4.5 | 4.0–4.5 (<1 kg) 3.5–4.0 (1–1.8 kg) | 3.0–4.3 |
| Lipids, g | 4.8–6.6 | 4.8–6.6 | 5.3–6.8 |
| Carbohydrate, g | 11.6–13.2 | 11.6–13.2 | 11.5–15 |
| Sodium, mg | 69–115 | 69–115 | 46.8–75.6 |
| Potassium, mg | 78–195 | 66–132 | 72–192 |
| Calcium, mg | 120–200 | 120–140 | 148–222 |
| Phosphorus, mg | 60–140 | 60–90 | 98–131 |
| Vitamin D, IU | 400–1000 per day (from milk + supplement) | 800–1,000 per day (milk to provide 100–350 per 100 kcal) | 90–324 |
| Vitamin A, mcg RE | 400–1,100 | 400–1,000 | 245–456 |
| Zinc, mg | 1.4–2.5 | 1.1–2.0 | 1.32–1.8 |
| Iron, mg | 2–3 | 2–3 | 2–3.6 |
| Iodine, mcg | 10–55 | 11–55 | 7.2–42 |
Preterm Infant Enteral Nutrition Management
Human Milk Fortification
While maternal human milk is the gold standard for feeding preterm infants, it is unable to provide the appropriate combination of macro- and micronutrients or support growth when fed at typical volumes of 135 to 200 mL/kg. Therefore human milk fortification has become the standard of care for preterm infants to help promote short-term growth in the hospital. A multinutrient human milk fortifier provides crucial nutrients including protein, essential fatty acids, calcium, phosphorus, vitamin D, zinc, and electrolytes and increases the caloric density of human milk. The combination of nutrients is critical to support growth of lean body mass and developing organs, including the lungs and rapidly growing brain. Commercial formula companies have improved human milk fortifiers during the past decades with regard to protein and nutrient content and currently market products that are available in both powder and liquid. Liquid is often preferred because it can be sterilized, but it is not universally accessible. The first liquid bovine human milk fortifier was acidified as a method to preserve nutrient composition while reducing heat treatment required to achieve sterility, although nonacidified preparations are now available. Nonacidified bovine human milk fortifiers are preferred because infants exhibit less metabolic acidosis, less feeding intolerance (emesis or gastric residuals), and improved growth compared with acidified bovine human milk fortifier. One version of bovine fortifier has extensively hydrolyzed protein as the protein source to aid in digestion, although there was no difference in feeding intolerance compared with intact protein. The amount of protein in bovine human milk fortifier varies both among and within manufacturer product lines ( Table 19.9 ). The ideal amount of protein to add to human milk is unknown, though small improvements in weight gain are seen during hospital admission with fortifiers that provide an additional ≥1.4 g protein per 100 mL of human milk compared with moderate protein amounts (≥1–<1.4 g per 100 mL human milk).
