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Enteral nutrition
Evidence is increasingly accumulating that nutritional inadequacies in the early neonatal period have both short- and long-term consequences. Nonetheless, provision of adequate nutritional support to the high-risk premature infant remains a significant clinical challenge. Among extremely premature infants, duplicating rates of in utero growth remains an elusive goal and postnatal growth failure remains a common complication of neonatal intensive care. This chapter contains exercises designed to help those who care for premature infants to review enteral nutrient requirements, identify strategies to optimize provision of nutrition, and describe the importance of adequate postnatal growth. In addition, areas where further research is needed to determine optimal nutritional support to improve outcomes in this population are emphasized.
Nutrient requirements
The current recommendations for enteral nutrient intake for very low birth weight (VLBW; less than 1500 g) premature infants are presented in Table 7.1 . These recommendations are based on current evidence and consensus of an expert panel. It is important to recognize that a combination of both parenteral and enteral nutrition is needed during the early phase of nutritional support of premature infants to avoid nutrient deficits that contribute to postnatal growth failure. Fortification of human milk (both maternal and donor) is also necessary to meet these nutrient requirements to support optimal growth and outcomes. Although meeting these recommendations can be particularly challenging in extremely low birth weight (ELBW) infants, standardized feeding protocols have been shown to be associated with improved outcomes in this population, including the number of days to reach full enteral feedings and the number of days of total parenteral nutrition.
TABLE 7.1
Recommended Enteral Intakes for Premature VLBW Infants
Adapted from Koletzko B, Poindexter B, Uauy R, editors: Nutritional Care of Preterm Infants Scientific Basis and Practical Guidelines, Vol. 110, 2014, World Review of Nutrition and Dietetics Karger.
| Nutrient | per kg/day | per 100 kcal |
|---|---|---|
| Fluids, mL | 135–200 | - |
| Energy, kcal | 110–130 | - |
| Protein, g | 3.5–4.5 | 3.2–4.1 |
| Lipid, g | 4.6–6.6 | 4.4–6 |
| Carbohydrate, g | 11.6–13.2 | 10.5–12 |
| Calcium, mg | 120–200 | 109–182 |
| Phosphate, mg | 60–140 | 55–127 |
| Iron, mg | 2–3 | 1.8–2.7 |
| Vitamin D, IU | 400–1000 | - |
These recommendations for nutrient intake are for most stable, growing VLBW infants. An individualized approach to account for nutrient deficits, disease factors such as bronchopulmonary dysplasia or necrotizing enterocolitis (NEC), rate and proportion of both weight gain and linear growth, and the predominant source of enteral feeding may necessitate adjustment to meet the needs of some infants. It is important to point out that energy requirements are lower (85–95 kcal per kg/day) if the infant is receiving parenteral nutrition. Although most clinicians focus on daily enteral intake in terms of volume (mL per kg/d) or calories (kcal per kg/d), protein intake should be carefully considered, as inadequate protein intake is associated with poor growth and adverse neurodevelopmental outcomes in ELBW infants. A comparison of estimated protein intake is shown in Table 7.2 . As will be discussed later in this chapter, erroneous assumptions made about the nutrient content of human milk before the addition of fortifier or after handling and storage may inadvertently result in suboptimal nutrient intake (especially energy and protein).
TABLE 7.2
Protein Intake With Enteral Feedings at 150 mL/kg/d
| Protein (g/kg/d) | |
|---|---|
| Donor human milk (assume 0.7–1 g/dL) | 1.05–1.5 |
| Preterm human milk (assume 1.4–1.6 g/dL) | 2.1–2.4 |
| Preterm human milk + human milk fortifier (24 kcal/oz) | 3.5–4.5 |
| Preterm formula (24 kcal/oz) | 3.6–4.3 |
| Transitional/postdischarge formula (22 kcal/oz) | 3.1 |
| Term formula | 2.1 |
Initiation and advancement of enteral nutrition
Case 1
A 27-week gestation female is delivered by cesarean section because of worsening maternal preeclampsia. Her birth weight is 635 g. She was placed on bubble continuous positive airway pressure (CPAP) in the delivery room and has been stable overnight on less than 30% supplemental oxygen. Upon her admission to the NICU, starter parenteral nutrition (PN) with 10% dextrose and 3 g/kg/day of intravenous amino acids was initiated through an umbilical venous line. On rounds, her bedside nurse inquires as to when the baby will start to receive enteral feedings.
Exercise 1
Question
- 1.
Which of these statements reflects an evidence-based decision related to the initiation of enteral feedings in this infant?
- A.
PN is supplying the infant with all necessary nutrients; enteral feeding should be delayed until the infant is no longer at risk of developing NEC.
- B.
Feedings should not be initiated until the umbilical line is removed.
- C.
Feedings can be initiated using half-strength premature formula.
- D.
Enteral feedings (10–20 mL/kg/day) with human milk should be initiated today.
- A.
Answer
- 1.
D. Although the infant is receiving a reasonable intake from PN, it is important that consideration is given to beginning enteral feedings as early as possible. There are known benefits of early enteral feedings in premature neonates, and conversely, potential detriment to postnatal intestinal adaptation with a prolonged absence of any enteral feedings. If maternal milk is not available, donor human milk can be used so that the initiation of enteral feedings is not delayed. The presence of an umbilical line does not preclude the initiation of low-volume enteral feedings. Furthermore, there is no evidence to support the use of diluted or half-strength formula as an effective strategy to decrease the risk of NEC.
Initiation of enteral nutrition
Decisions related to introduction and advancement of enteral feedings present several dilemmas for clinicians and have the potential to have an impact on important morbidities such as NEC and late-onset sepsis. Although the fear of NEC has historically driven a delayed approach to enteral feeding, there are a number of reasons to recommend early initiation of enteral nutrition in premature infants. In a piglet model of neonatal nutrition, a delay in enteral feedings resulted in a decrease in cell proliferation in the small intestines, a decrease in superior mesenteric artery blood flow, and an increase in apoptosis.
Minimal enteral feedings, also known as trophic feedings, are typically defined as low-volume (less than 24 mL/kg/day initiated within 96 hours of birth and continued for 1 week) feedings that do not provide sufficient calories to support somatic growth but help to promote maturation of the structure and function of the premature intestinal tract (also known as “gut priming”). Few studies have specifically evaluated the effect of early trophic feeding versus a similar duration of enteral fasting in ELBW or VLBW infants. The most recent Cochrane review included nine trials with a total of 754 VLBW infants (and very few ELBW infants included); this metaanalysis found no evidence of benefit or harm of early trophic enteral feeding, including no difference in the incidence of NEC.
Having a standardized feeding protocol for VLBW that includes initiation of enteral nutrition within 6 to 48 hours of birth has been associated with improved outcomes, including a reduction in the number of days of parenteral nutrition, a reduced risk of NEC, and reduced rates of late-onset sepsis. Indeed, a risk factor for progression from medical to surgical NEC is having never received any enteral feeding.
The presence of umbilical lines, including an umbilical arterial catheter, is not a reason to withhold enteral nutrition. Current evidence has not supported the theoretical concern of the umbilical catheter reducing intestinal blood flow or increasing medical complications during trophic feedings. In addition, the common practice of withholding enteral feedings during treatment for a patent ductus arteriosus has recently been called into question. A randomized clinical trial demonstrated that continuation of trophic feedings at 15 mL/kg/d during treatment with indomethacin versus no enteral feedings resulted in fewer days to achieve full enteral feedings (defined as 120 mL/kg/d) with no increase in complications including NEC or spontaneous intestinal perforation.
If available, expressed maternal milk should be provided as the initial feeding. The initiation of early enteral nutrition should not be delayed until maternal milk is available; donor human milk can be used as a bridge until maternal milk supply is established. Several clinical studies have demonstrated reductions in the number of days to achieve full enteral feeding, total number of days that enteral feeds are withheld, and days of hospital stay. Oral colostrum care is not a substitute for minimal enteral nutrition.
Advancement of enteral nutrition
There is no universal consensus on the optimal rate of advancement of enteral feedings in ELBW and VLBW infants. The rate of advancement is one potentially modifiable risk factor—with too rapid of feedings being associated with NEC and sustained level of trophic feedings or too slow of advancement resulting in longer time to full enteral feedings and prolonged use of central venous lines and parenteral nutrition. Neither early versus late initiation of enteral feedings nor slow versus fast enteral advancement were shown to reduce NEC as summarized in recent systemic reviews. Several studies have shown a decrease in the incidence of NEC with the implementation of standardized feeding protocols.
Investigators in the United Kingdom have recently completed the speed of increasing milk feeds trial (SIFT; NCT01727609). Approximately 2800 VLBW infants were enrolled in this multicenter trial, and infants were randomized to slower or faster (18 versus 30 mL/kg/day) advancement of feedings until they reached full milk feedings (defined as 150 mL/kg/d). The primary outcome is survival without moderate or severe neurodevelopmental disability at 24 months corrected age. A published report of these data is pending but will be critical in confirming in VLBW infants the short-term benefits previously reported of a faster feeding advancement and adding to the literature that practice is without potential harm.
A recent randomized clinical trial evaluated early progressive feeding (without a period of trophic feeding) and delayed progressive feeding after a 4-day course of trophic feeding in 60 ELBW infants. The primary outcome was the number of full enteral feeding days in the first month after birth; infants randomized to early progression of feeding were found to have a 2-day advantage in the number of full enteral feeding days and a reduction in the number of days of parenteral nutrition. Of note, these investigators found no difference in the composite outcome of NEC or death between groups, although the study was not adequately powered to detect a difference in NEC.
Intrauterine growth restriction (IUGR)
According to the 2013 Fenton Growth Curve, the birth weight of the infant in this case is at the 9th percentile and is thus considered growth restricted. IUGR infants have an increased risk of NEC. As a result, it is common practice to delay initiation of enteral nutrition to theoretically reduce the compromise to an already perceived compromised gut. However, this strategy is not evidence-based and has been challenged in several studies. A delay in the initiation of enteral feedings (>48 hrs) in growth-restricted infants with abnormal umbilical artery Doppler waveforms did not lead to a lower risk of NEC; in contrast, feedings initiated within 48 hours reduced the time to full enteral feedings (with a concomitant reduction in the days requiring parenteral nutrition) and reduced the risk of cholestasis. This has been recently confirmed in a cohort of 62 growth-restricted babies in which early versus late enteral feeding had earlier discontinuation of PN and time to regain birth weight without an increase in NEC incidence.
Human milk
Case 2
The attending obstetrician requests an antenatal consult for a 26-year-old primigravida who has presented at 24 weeks estimated gestational age with premature labor with rupture of membranes and imminent delivery.
Exercise 2
Question
Which of the following statements regarding provision of human milk to premature infants should be included in the consult?
- 1.
Mother’s own milk supports the preterm infant’s developing immune system.
- 2.
Premature infants who receive their mother’s own milk have a lower incidence of sepsis and NEC.
- 3.
Premature infants who receive mother’s own milk demonstrate improved developmental outcomes compared with formula-fed premature infants.
Answer
All of the above statements are true.
Given these and other important benefits, the use of mother’s own milk should be encouraged for all premature infants. The use of mother’s own milk as the primary diet for preterm infants was affirmed in policy statements from the American Academy of Pediatrics and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).
Several studies have demonstrated the immunologic benefits of human milk for premature infants, including higher concentrations of secretory IgA, lysozyme, lactoferrin, and interferon in preterm human milk. Provision of mother’s own milk may also enhance colonization of the infant’s intestinal tract with beneficial commensal organisms. The incidence of infection, bronchopulmonary dysplasia, and NEC are decreased in preterm infants who receive mother’s own milk. In addition, observational studies in ELBW infants have shown an association between exposure to mother’s own milk and improved neurodevelopmental outcomes at 18 to 22 months’ corrected age and at preschool age (30 months). The number of days in the first postnatal month that an infant received >50% breast milk was positively correlated with deep nuclear gray matter volume at term equivalent and cognitive and motor outcomes at 7 years of age. In another study, maternal milk was also found to decrease the need for rehospitalization between NICU discharge and 30 months’ corrected age.
It is important to recognize that many mothers who deliver prematurely will choose to express milk for their infant once they are properly informed of the numerous benefits. All caregivers providing care to ELBW and VLBW infants should be knowledgeable with respect to the many benefits of mother’s own milk and must be committed to ensuring that all mothers in their care are equipped to express their breast milk. Many units have successfully implemented quality improvement initiatives to increase human milk usage in preterm infants.
Case 3: Banked donor human milk
After observing your conversation with the mother, the neonatal nurse practitioner in the NICU asks your opinion regarding the use of banked donor human milk if the mother is unable to provide enough milk for her infant.
Exercise 3
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