International perspective: Management of nutrition in preterm infants in settings with limited resources

Key points

1.
Globally it is estimated that 15 million infants are born preterm and most of them are delivered in low- and middle-income countries. Nutritional interventions may be costly, increasing the financial burden of their care, or may be unavailable.
2.
Kangaroo Mother Care is promoted for reducing morbidity and mortality in preterm/low-birth-weight infants.
3.
Mother’s own milk is the preferred source of nutrition for preterm infants. Support should be given to mothers to breastfeed (in cases where the preterm infant is of sufficient maturity) or to express their milk.
4.
Human milk may need to be pasteurized if the mother is HIV positive; refrigeration is not available and expressed milk needs to be kept at room temperature; or donor milk is being used. Heat-flash pasteurization is an option for limited-resource settings where other methods such as Holder pasteurization are not available.
5.
Human milk alone may not meet the nutritional needs of very preterm infants. Options for improving the delivery of nutrients and approaching the recommendations for this population in low-resource settings include fortification (with human milk fortifiers if available or with preterm formula); use of supplements (calcium, phosphate, vitamins, zinc, oils, other); early start and advancement of enteral feeds; or increasing the volume of enteral feeds up to 300 mL/kg/d of expressed human milk. The chosen option may depend on cost and available resources; however, optimal results are not always achieved with these strategies. Further research is needed for this vulnerable population.
6.
During the transitional period from gastro-enteral to oral feeds, the World Health Organization recommends feeding with a cup, palladai, or spoon. The use of palladai has been associated with better weight gain, faster achievement of full feeds, and shorter length of hospital stay versus the use of other cups. Finger feeding is an additional strategy that has been associated with fewer complications and lower milk loss versus cup feeding.
7.
Other supplements used in low-resource settings include emollient oils applied on the skin and oral probiotics. More research is needed in this area.

Introduction

Globally it is estimated that 15 million infants are born preterm and most of them are delivered in low- and middle-income countries ; in these settings, 32.4 million infants (term and preterm) are born small for gestational age (SGA). Fig. 12.1 shows increasing trends for estimates of preterm birth rates from 2000 to 2014 globally and in nearly all regions. Good nutrition is critical for these infants to improve not only survival but short- and long-term health outcomes. Many challenges are encountered when trying to achieve this goal as preterm infants are immature and need nutritional interventions that may be costly, increasing the financial burden of their care, especially in low-resource settings. It is therefore important to understand different practices used in these settings, which may be based on a limited and low or very low quality of evidence. Research is urgently needed to provide these preterm infants with the best possible nutritional care.

Fig. 12.1, Regional and global estimates of preterm birth rates (% of live births) from the years 2000, 2005, 2010, and 2014. For reference, total live births for each year globally are 129.6 million, 133.2 million, 137.8 million, and 139.9 million for the years 2000, 2005, 2010, and 2014, respectively.

In this chapter we will describe strategies used in some low-resource settings to increase nutrient delivery to preterm infants, feeding interventions to improve the transitional period between gastro-enteral and oral feeds, and a low-cost pasteurization technique.

Enteral feeding strategies to improve the nutritional status of preterm infants

Mother’s own milk, the preferred source of nutrition for all infants, has multiple benefits including improved survival and immune defense; lower incidence of morbidities, especially necrotizing enterocolitis (NEC); better digestion of nutrients; and better neurodevelopmental outcomes, among others. ^, Promoting milk production and maintaining adequate milk supply is an important consideration for mothers who are feeding human milk (HM) to their infants and may be especially so for mothers of preterm infants. Initiation of lactation in mothers of preterm infants may be compromised compared to mothers of term infants and may display greater variability between mothers of preterm infants.

Kangaroo Mother Care (KMC) , whereby an infant has skin-to-skin contact with their mother by being held vertically between the breasts and underneath clothing, is associated with frequent and exclusive/near exclusive breastfeeding in preterm and/or low-birth-weight infants. KMC is primarily promoted in resource-limited settings for reducing morbidity and mortality in preterm/low-birth-weight infants; immediate KMC is now recommended, unless the infant is in shock or unable to breathe spontaneously. ^,

Research into KMC focuses mainly on initiation and/or exclusivity of feeding at the breast (i.e., breastfeeding) but generally does not consider initiation of lactation per se by the mother when an infant is unable to feed at the breast. The degree of prematurity will influence the ability of an infant to latch and feed at the breast and mothers may need to express their milk. In developed nations, electric breast pumps for expressing HM are readily available, but in resource-limited settings mothers may need to express with a manual breast pump or express manually by hand. A Cochrane review in 2016 indicating effective strategies to support expression of HM included early expression of milk soon after birth, relaxation, massaging and warming the breasts, manual hand expression, and use of low-cost pumps. This review also suggested that some of these measures may influence nutritional content of the expressed HM in addition to influencing volume. For example, the protein content was higher when using hand expression or electric pumping versus manual pumping; higher sodium and lower potassium were reported for hand expression over either manual or electric pumping; and breast massage while pumping resulted in higher fat/lipid content. Alternatively, no difference in energy content was reported between methods of HM expression. Whichever method is chosen, it is important to consider cost, availability, and preference, and that each mother is taught how to express successfully, with appropriate instruction on hygienic handling and storage of expressed HM to prevent contamination.

HM alone may not meet the nutritional requirements of very preterm infants, and HM should be fortified or enriched to improve the growth and micronutrient status of preterm infants. As HM composition varies between mothers and can be influenced by their dietary intake (particularly for micronutrients), published region-specific macro-/micronutrient values for HM should be used wherever possible when calculating fortification needs.

Fortification of HM has been adopted by most countries with high-income economies, but this may not be practical in low-resource settings because of cost, availability, and risk of infection if not handled properly. Explorations of different strategies to increase the nutrient intake of very preterm infants in low-resource settings have been reported. Parenteral nutrition (PN) is not universally available; thus it is critical to start an adequate volume of enteral feeds as soon as medically suitable. It is also important to understand the maximum volume of enteral feeds tolerated by very-low-birth-weight and extremely low-birth-weight infants to deliver nutrients approaching recommend amounts, or at least higher levels of nutrients in conditions where fortification is not possible. Furthermore, it is important to understand the supplements used in low-resource settings to enrich HM when fortifiers are not available. In this section we will discuss some studies that have alluded to these challenges and will focus on:

Early initiation and advancement of enteral feeds
Increasing the volume of enteral feeds
Use of supplements, formulas, or fortifiers to enrich HM

Early initiation and advancement of enteral feeds

An unblinded randomized controlled trial conducted in India allocated 180 stable preterm infants (1000–1499 g) to receive either early total enteral feeding (ETEF) from day 1 of life, with 80 mL/kg/d and advancing to 180 mL/kg/d with no intravenous fluids; or conventional enteral feeding (CEF) starting at 20 mL/kg/d on day 1 of life and advancing 20 to 30 mL/kg/d with intravenous fluids (no PN); this group also advanced to 180 mL/kg/d. The ETEF group reached full enteral feeds more quickly (−3.6 days) and had a lower incidence of sepsis (26% vs. 60.6%), less feeding intolerance (15.9% vs. 30.2%), and shorter length of hospital stay (−4.1 days) versus the CEF group. The incidence of NEC was similar. At 1 month of age, infants in the ETEF group were significantly heavier (~100 g) than the CEF group. Results suggest this strategy of ETEF might be safe and may also offer benefits in settings with limited resources. Further research is needed to understand whether these findings could be translated to other populations, especially for unstable or extremely low-birth-weight infants.

Increasing the volume of enteral feeds

The intake of enteral feeds up to 200 mL/kg/d may increase the delivery of macro- and micronutrients as well as caloric intake in preterm infants receiving unfortified HM versus those receiving lower enteral intakes (150–160 mL/kg/d). Moreover, volumes up to 300 mL/kg/d may further increase the nutrient intake of preterm infants. A prospective trial conducted in India compared outcomes in 64 very-low-birth-weight infants randomized to receive either 200 or 300 mL/kg/d of expressed HM and followed these infants until they reached 1700 g. Although increased volume of intake resulted in an estimated increase in caloric intake (134 vs. 200 kcal/kg/d), protein (2.2 vs. 3.3 g/kg/d), calcium (68 vs. 102 mg/kg/d), and phosphorus (30 vs. 45 mg/kg/d), values still fell short for some current nutrient recommendations for this population, particularly for micronutrients. Daily weight gain was significantly higher (24.9 vs. 18.7g/kg/d, p < 0.0001) in the group receiving 300 versus 200 mL/kg/d, and importantly, there were no differences in complications or feeding tolerance. Of note, this study was small. In infants assigned to 300 mL/kg/d, 12 of 30 participants received less volume than targeted and 40% of infants had high levels of alkaline phosphatase (expected as the intake of calcium and phosphorus were below recommendations), which may underscore the importance of not only looking at gain in weight but also bone health and other markers of micronutrient status in these infants. A subgroup analysis of SGA infants in this study showed no effect on weight gain with this high-volume strategy.

Other studies have compared different volume intakes (from 140 to 200 mL/kg/d) in very preterm infants ^, and in general, weight gain was increased in the groups with higher volume intakes. One study conducted in the United States included larger but very preterm infants (1001–2500 g) receiving fortified HM. Higher volume intakes were associated with increased length, head circumference, and mid-arm circumference in infants receiving 180 to 200 mL/kg/d versus 140 to 160 mL/kg/d, at 36 weeks gestational age or at discharge; adverse effects were similar between groups.

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