What are the signs of adequate nutritional intake for a breastfed infant?
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Breast milk also contains important non-nutritional components, such as antimicrobial factors, digestive enzymes, hormones and growth factors that are important for passive protection against infections and immune-mediated diseases and modulate immunological development. Immune-related components and growth factors include:
5. How long should an infant be exclusively fed breastmilk? Breastmilk can be provided exclusively for around the first 6 months, meeting all of the Infants nutritional needs. Breastmilk is still very important beyond the first 6 months. Once solids are introduced breastmilk continues to provide important nutrients and growth factors up to 2 years. The WHO recommends breastmilk continue to be part of the young child’s diet, to 2 years of age and beyond. The needs of infants determine the amount of nutrition required to maintain and support adequate growth and optimal health while maintaining homeostasis with other nutrients. Nutritional requirements vary in infancy, and growth patterns are closely linked to optimized nutrition. The use of standardized definitions is essential when plotting growth in infancy. Energy expenditure for basal metabolic processes, regular physical activities, as well as unexpected increased energy utilization for pathological conditions, determine the infant's caloric intake. A healthy child from birth to 1 year should receive around 100 kcal/kg/day. Neonatal caloric requirements are higher at about 110–135 kcal/kg/day.[7] Of the total energy requirement, a healthy infant utilizes about 40-60 kcal/kg/day for basal metabolic rate. Thermoregulation plays a massive role in early infancy, requiring a significant amount of energy expenditure. This is even higher in smaller preterm infants with minimal subcutaneous fat stores. Feeding, digestion, absorption, storage, and elimination also require a vast amount of energy, often up to 30-50 kcal/kg/day. Preterm and sick infants often require higher amounts of energy to maintain adequate growth. As infants get older, their energy requirements decrease, with boys requiring more than girls usually on account of weight.[8] Nutritional needs are objectively defined collectively using the term 'dietary reference intakes.'[9] Estimated average requirements (EAR) refers to the minimum amount of a nutrient that is required to meet the needs of half the population. Since EAR only covers about half of the population, a 20% higher limit is used as recommended dietary allowances (RDA). RDA refers to a sufficient amount of average daily dietary intake that meets the nutrient requirement for most of the healthy population at a particular stage. Adequate intake (AI) is the acceptable range of nutrient intake based on healthy populations in cases with inadequate evidence to use EAR or RDA. Tolerable upper intake levels (UL) are the highest levels of nutrient intake that are acceptable without causing adverse effects.[9] In situations requiring close monitoring of infant growth, nutrient requirements can be measured using these parameters to maintain an objective log of nutrient intake during periods of growth faltering. Nutrient Profiles: Macronutrients Macronutrients include large nutrient molecules that provide the primary nutritional source of energy and substrate, playing a vital anabolic role in building tissues and in growth. These are broadly grouped into proteins, carbohydrates, and fats. Proteins Proteins are building blocks that play a significant anabolic role in building muscle and tissues. Protein accounts for about 15% of total energy intake. Structurally, proteins are large molecules comprised of chains of amino acids joined by peptide bonds. They can be classified based on the number of amino acids in the protein chain into dipeptides, oligopeptides, or polypeptides. Complex folding of the longer protein chains into three-dimensional structures further results in a tertiary modification, adding complexity to the protein structure. Enteral protein intake in neonates is primarily consumed as whey or casein proteins. Whey protein has less methionine content, while casein has less cysteine content. Mucins are another minor group of human milk proteins, seen in milk fat globule membranes.[10] Breastmilk is an excellent source of protein with a whey: casein ratio of 80:20, even up to 90:10 in colostrum.[10] The protein ratio changes to 55:45 in mature milk while still retaining the predominance of whey protein. The bioavailability of protein in breastmilk is higher, accounting for better protein absorption and retention in breastmilk fed infants. The protein content in formulas is included as a combination of whey and casein with varying ratios in different formulas. Once ingested, protein molecules are broken down into peptides and amino acids, which are then recycled to form new proteins. Enterocytes play a significant role in absorbing peptides and free amino acids. Amino acids (AA) are utilized to a certain extent directly by the gut itself. Parenteral intake of protein, on the other hand, is achieved using various amino acid formulations. Amino acids have historically been classified as essential and non-essential based on the maintenance of nitrogen balance or based on a varying degree of 'essentiality' considering supply and demand.[11] Effectively, the amino acids with structures that cannot be synthesized from other amino acids are considered essential in nutrition. These include, at the very least, methionine, threonine, tryptophan, branched-chain amino acids (valine, leucine, isoleucine), phenylalanine, histidine, and lysine. The absorbed protein is distributed widely all over the body, primarily in muscle and gut, with the protein distribution also varying by age. Proteins provide four calories per gram and are not to be relied upon as a significant source of calories. Often when calculating nutrition from parental nutrition, it is divided out into protein and non-protein calories. Adequate carbohydrate content is essential to ensure the protein is used for anabolic purposes to build tissue rather than being used to provide calories. Lipids (Fats) Lipids are a primary source of caloric intake, primarily in the form of triglycerides, free fatty acids, and cholesterol. Lipids account for about 40-50% of total energy intake. The caloric density of lipids is 9 kcal/g. During the fetal period, lipids are transferred transplacentally as fatty acids, gradually increasing in the third trimester. Body fat stores are accumulated towards the end of the third trimester, provide a significant source of energy to the newborn infant. Stores are decreased in low birth weight and preterm infants. Excess glucose is also converted to lipids by lipogenesis. Triglycerides account for the bulk of lipids accounting for up to >90% of all lipid intake, with phospholipids and cholesterol acting as minor sources usually packaged into milk-fat globules. Enterocytes utilize the ingested lipids to produce lipoproteins rich in triglycerides, known as chylomicrons, that are used for transporting lipids via lymphatics to the target cells.[12] Chylomicrons in cord blood and at one-month-old preterm infants have been shown to have higher cholesterol than in term infants, resulting in a lower chylomicron triglyceride-cholesterol ratio in preterm infants compared to term infants.[13]Triglycerides are broken down by lipases into fatty acids, which can be classified into essential and non-essential fatty acids. Essential fatty acids (EFA) include linoleic (LA) and alpha-linolenic acid (ALA), which provide an essential source of fats. Besides, given the current use of intravenous lipid emulsions, arachidonic acid (ARA) and docosahexaenoic acid (DHA), derivatives of LA, and ALA, respectively, are also considered EFAs. Essential fatty acid deficiency (EFAD) can appear as soon as 7-10 days if not receiving adequate lipid intake. EFAD can be diagnosed biochemically using the triene:tetrene ratio (Holman index) with a value greater than 0.2 suggestive of biochemical EFAD, although symptoms appear >0.4.[14] The triene:tetrene ratio does not take into consideration omega-3 fatty acids. Long-chain polyunsaturated fatty acids (LC-PUFA) are essential for retinal and brain development, thus impacting neurodevelopmental outcomes that often can last much beyond the period of undernutrition. Medium and short-chain triglycerides (MCT) are easier to absorb than LC-PUFA, thus providing excellent sources of energy. Preterm breastmilk has higher MCT content. MCT oil can be used in children to supplement fat calories in certain circumstances. Parenteral lipids are most commonly given as intravenous lipid emulsions. Multiple such emulsions have been used in infants over the past fifty years. Intralipids are currently the most widely used fat emulsions made from soybean oil, commonly used at 20% concentration.[15] These include a combination of omega-3, omega-6, and omega-9 fatty acids. ARA is a metabolite of omega-6 fatty acids, which results in a pro-inflammatory profile. In contrast, omega-3 fatty acids are converted to eicosapentaenoic acid, which upon further breakdown, results in a less pro-inflammatory profile. Phytosterols are plant-derived lipid molecules similar to cholesterol, seen at high concentrations in soybean oil derived lipid emulsions. These have high omega-6 FA concentration, which has been linked to increased pro-inflammatory activity, decreased cell-mediated immunity, and an increase in retinopathy of prematurity.[16] A newer generation lipid emulsion is SMOF (a mixture of soybean, MCT, olive oil, fish oil), which is approved for adults but being utilized in the neonatal ICU more commonly for infants with or at risk for parenteral nutrition-induced cholestasis (PNAC). Infants and children with PNAC may be candidates to receive Omegaven; a fish-oil derived intravenous lipid emulsion, rich in omega-3 fatty acids, therefore with a less inflammatory omega-3:omega-6 ratio. This has been associated with less hepatotoxicity and less inflammation. Despite theoretical concerns of increased risk of bleeding due to metal toxicity from fish oil, this has not been clinically validated. Omegaven is FDA approved for use in pediatric patients with PNAC. The recommended dose of Omegaven is 1 g/kg/day.[17] Clinolipid is a soybean-olive oil mix with a favorable lipid profile that is used in Canada and was recently approved the US food and drug administration (FDA). Medium-chain triglycerides (MCT) are not used as an emulsion since it is coconut oil-based, has no EFA and is cleared quickly from circulation. Infants receiving intravenous lipid emulsions require close monitoring using liver functions, and triglyceride levels (to maintain a goal TG level <250 mg/dL). Carbohydrates (Energy) The primary source of carbohydrates to the brain is glucose. Carbohydrates provide the bulk of calories with 40-55% of daily needs. While carbohydrates are utilized as disaccharides, oligosaccharides, and polysaccharides, lactose forms the primary enteral source of glucose in human milk and standard infant formula. The amount of carbohydrate requirement is calculated based on the total anticipated energy requirement taking into account the energy from non-carbohydrate sources. Besides, glucose provides the carbon molecules required for synthesizing fatty acids and amino acids. In parental nutrition, it is often started as D10W and increased over days accounting for the glucose infusion rate (GIR). Dextrose provides 3.4 kcal/g of glucose. Micronutrients and Other Trace Elements Nutrient elements that are required in minute quantities are considered micronutrients or trace elements- with RDA often in micrograms. The most common micronutrients are zinc, copper, chromium, manganese, and selenium. Trace elements require age, size, and disease-specific adjustments in the pediatric population; therefore, adult recommendations cannot be used. While the absorption of trace elements is tightly regulated in the gastrointestinal tract, supplying trace elements parenterally bypasses this homeostatic barrier leading to a risk of overload if excessive quantities are provided.[18] Iron: Iron is a basic component of hemoglobin and myoglobin and is hence an essential nutrient. The deficiency of iron results in microcytic anemia and FTT. Growing preterm infants require a higher dose of iron to meet the demands of catch up growth and to support increased red blood cell production from bone marrow proliferation. Breastfed infants may require iron supplementation after 4-6 months of life where formula-fed infants do not as infant formula is fortified with iron. Zinc: Zinc is a vital cofactor of human enzymes and is considered essential for growth. Zinc requirements vary with age and clinical condition. Infants with short bowel syndrome often have increased fluid losses; therefore are at higher risk of zinc deficiency. Premature infants need higher doses of zinc secondary to their rapid growth. Zinc deficiency can result from congenital or nutritional causes. Congenital abnormality of zinc absorption or transport results in acrodermatitis enteropathica affecting skin, hair, and nails, and patients present with FTT, hair loss, diarrhea, dermatitis, facial rash, and nail hypoplasia. Acquired/ nutritional deficiency of zinc is commonly seen in preterm infants on PN, resulting in growth failure, poor wound healing, skin rashes, and iron deficiency anemia as zinc is a cofactor in iron metabolism.[18] Copper: Copper plays an important role as a cofactor to over twenty enzymes involved in multiple basic cellular processes involving cellular respiration, iron metabolism, and production of red blood cells, to name a few.[19] Copper deficiency is rarely seen. The increased requirements, limited stores, and potential increased gastrointestinal losses of copper must be balanced against the reduced biliary excretion in preterm babies.[18] Iron deficiency is one of the earliest signs of copper deficiency and may present with anemia, neutropenia, FTT, etc. Copper is no longer recommended to be held routinely in infants with cholestasis (PNAC) due to the risk of microcytic anemia. Chromium: Chromium plays a crucial role in insulin metabolism, thus regulating glucose levels. While deficiency of chromium has not been well reported in humans, chromium toxicity is well known, especially in infants and children on long-term PN. Chromium is believed to have renal tubular toxicity with a reduced glomerular filtration rate. Given the wide variability in the contamination of chromium with different PN formulations, the actual intake is often unclear. It is thus recommended to decrease the dose of chromium in children with renal failure, but not eliminate it.[18] Manganese: Manganese is an important trace element with a role in enzyme activation and function of multiple enzymes, including metalloenzymes with manganese incorporated into the enzymatic molecular structure, most notably, superoxide dismutase enzyme. However, due to wide availability in nature, deficiency of manganese is rare. However, the neurotoxicity and hepatic toxicity of manganese are well described. In preterm infants on long-term PN, and especially those with PNAC, the risk of accumulation and, thus, toxicity is significantly higher since manganese is primarily excreted via the liver. Thus manganese is no longer added as a trace element as it can be neurotoxic in large amounts, and there is enough in the PN additives.[18][20] Selenium: Selenium is an antioxidant associated with reductions in a wide range of pathological conditions in infants, especially preterm infants on PN, including bronchopulmonary dysplasia/chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity, periventricular leukomalacia and sepsis. As a cofactor for glutathione peroxidase enzyme, selenium plays a role in reducing free radicals, thus decreasing cellular level injury across various organ systems. Due to predominantly renal excretion, caution is recommended in infants with renal dysfunction.[18][21] Vitamins: Preterm infants are prone to vitamin deficiencies due to lower stores, increase requirements, and immature metabolic processes. The opposite is also true that these preterm infants are at higher risk for toxicity due to immature and compromised renal function. Fat-soluble vitamins include vitamins A, D, E, and K. Vitamin A (Retinol) is known to play an essential role in the growth and development of skin, eyes, bones, and pulmonary epithelium. It is thus implicated in chronic lung disease, photophobia, abnormal epiphyseal bone growth, and FTT. Vitamin E (tocopherol) has an antioxidant role in iron-induced hemolysis. Vitamin K plays a vital role in coagulation through carboxylation of prothrombin into its active form, thus essential in preventing hemorrhagic disease of the newborn. Vitamin D plays a crucial role in calcium and phosphorus metabolism in conjunction with parathyroid hormone. Vitamin D deficiency is associated with rickets, osteopenia of prematurity, and failure to thrive. Water-soluble vitamins B and C, on the other hand, require daily intake to meet their requirements. Preterm Infants Preterm infants are a unique population with specialized needs. The nutritional requirements of preterm infants are diverse and vary significantly with gestational age and stage of growth. The extrauterine growth velocities of preterm infants in the NICU frequently fall short of in-utero growth velocities at corresponding gestational ages. Neurodevelopmental outcomes are strongly linked to growth velocities in preterm infants.[22] In addition to managing their overall medical needs, optimizing nutrition is intended to bridge this gap and improve growth and, thus, health outcomes. Nutrition in this critical stage of life must focus on providing optimal caloric content and protein as well as focus on optimizing individual macronutrients, micronutrients, and electrolytes. It poses a continuing challenge to maintain preterm infants' nutritional requirements, requiring a team of specialists, including neonatologists, gastroenterologists, and dieticians. Parenteral Nutrition in Preterm Infants Parenteral nutrition is essential to those unable to tolerate sufficient enteral feedings for various reasons. Intravenous nutrition starts at birth and is gradually reduced as enteral feeds are introduced. The type of IV access dictates the concentrations of the components of intravenous nutrition. Parenteral nutrition is roughly divided out to 55% carbohydrates (dextrose), 15% protein (amino acids), and 30% fat (lipid formulations such as intralipids, SMOF, or Omegavan). Intravenous dextrose is the most common source of carbohydrates. Dextrose (10%) is used as the starting fluid in most situations, except the extreme preterm infants, who may require a lower dextrose concentration. Dextrose concentrations are titrated based on infant's needs, serum glucose levels, and glucose infusion rate. While up to 12.5% dextrose can be given safely via a peripheral venous catheter, higher concentrations require central venous access. Parental amino acids can be supplemented from the first day of life, even in preterm infants.[22] The importance of adequate protein intake earlier in infancy is increasingly recognized. Increasing protein supplementation is associated with increased length at discharge in premature infants. Parenteral nutrition requires frequent lab work. Enteral Nutrition in Preterm Infants Enteral feeds are introduced as soon as possible and advanced gradually until full feeds are attained. Colostrum care is practiced in many neonatal intensive care units (NICUs) across the world wherein colostrum is applied orally, acting as oral immune therapy.[23] This can even be used in sick infants who are unable to start enteral feeding, however, in accordance with unit specific feeding practices. Colostrum care is ideally done using freshly produced colostrum as stem cells in colostrum are known to degrade within about six hours. Colostrum care has been shown to reduce the time to achieve full enteral feeds by a mean of 2.5 days in a Cochrane review.[23] No other significant benefits or adverse events were identified. However, the quality of the evidence from the studies available for the review was considered low. Once ready to feed enterally, small volume starter feedings are given, starting at 10-15 ml/kg/day. These are considered 'trophic' and used for gut priming. Trophic feeds are introduced in the first 24 hours in most NICUs across the USA. The feeds are gradually advanced by 10-30 ml/kg/day to full feeds, ideally attained by 7 to 14 days. While there are no standard 'one-size-fits-all' recommendations for feeding preterm infants, the optimal suggested timeframe for achieving full enteral feeds is inversely proportional to the size of the infants- taking about 7-14 days in infants with birth weight 750-1500g. The use of donor breastmilk is currently subject to unit-specific practices. Once the infant is receiving about 75-80 ml/kg/day, breastmilk (either mother's or donor milk) may be fortified with human milk fortifiers to 24 calorie/ounce (cal/oz), with some units practicing a gradual increase in fortification to 22 cal/oz then 24 cal/oz. Standard infant formulas are between 19 and 20 kcal/oz, which is modeled after breastmilk. |
