Infant Nutrition Requirements and Options

Function

Nutritional Requirements and Energy Expenditure

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.

Issues of Concern

The clinical impact of nutrition during infancy is best understood by measuring growth accurately. An in-depth understanding of the nuances of breastfeeding, formula supplementation, use of specialized formulas are keys to ensuring adequate growth in infancy. Growth can often be interrupted by certain pathological conditions, like gastroesophageal reflux, constipation, milk protein intolerance or allergy, and lactose intolerance, often requiring dietary modifications.

Measurement of Growth and Growth Failure

Infancy is a period of rapid growth. Weight, length, weight for height, and head circumference (HC) are the primarily used markers for measuring growth rates in infants and children. Trends in growth patterns over time provide more valuable information than a single measurement. Growth rates increase during the third trimester of pregnancy, accounting for about 90% fetal brain growth occurring between 20 weeks of gestation and full term. The gray matter undergoes a 4-fold increase from 29-40 weeks of pregnancy while the white matter increases 5-fold, from 35-40 weeks of pregnancy. While HC less than 10% at eight months of age correlates with a cognitive, educational, and psychosocial delay at eight years old, better length growth is associated with higher cognitive scores at 24 months. In an ideal scenario, a weight gain of 15-20 g/day and a length increase of 1 cm per week is considered optimal until about 36 weeks.[24]

An infant within the normal percentile ranges (e.g., 10 to 90 percentile for weight) may be failing to thrive if the growth rate stalls over a while. This might be missed by taking a one-time measurement that falls within the acceptable range. The growth rate is the fastest in the first three months after birth, reaching about 30 grams per day. The growth rate subsequently slows down to about 15 grams/day by 3-6 months and about 10 grams/day from 6-12 months. The length and head circumference also increase rapidly in the first year of life, increasing by about 25 cm and 12 cm, respectively. This period of rapid growth is best captured by using the appropriate growth charts from centers for disease control (CDC) and WHO. The WHO growth charts are the primarily used charts for infants and children 0-24 months, while the CDC growth charts guide for children older than two years of age.[25] Furthermore, the WHO growth charts, last updated in 2006, were devised based on a diverse international population and are more applicable to infants that are breastfed, while CDC charts were based on formula-fed infants from the United States, and set higher standards for weight gain, making growth appear to fall short of the standards. Besides, specialized populations require tailored growth charts unique to their condition. Down syndrome, cerebral palsy, and Turner syndrome are examples of conditions that have their growth charts. Preterm infants use the Fenton charts to follow growth.[26][27][28] It is thus important to realize that normal growth doesn't always depict normal wellbeing, but rather provides a general snapshot of overall health and wellbeing. Altered nutrition often leads to growth faltering with abnormal growth patterns as a frequent consequence of nutritional deficiencies.

Breastfeeding

Breastfeeding is now much more than a medical issue- it transcends social, economic, cultural, and geographic realms. AAP recommends exclusive breastfeeding up to six months of age.[29] Also, continued breastfeeding is recommended, as other foods are introduced. Breastfeeding promotes mother-infant bonding and is known to improve maternal and child health.[29] Breastfeeding has also been shown to reduce upper respiratory tract infections, middle ear infections (23%), lower respiratory tract infections (72%), and diarrhea in newborns. It is also suggested to reduce the risk of asthma (up to 40% reduction), food allergies, SIDS (30%), inflammatory bowel disease (40%), type 2 diabetes (40%), and obesity.[29] On the mother's side, breastfeeding has been shown to delay the return of menstruation, and due to increased metabolic demands can help with faster return to pre-pregnancy weight. Besides, a reduction in breast cancer has been shown with a longer duration of total breastfeeding for more than 12 months.[29] If 90% of women in the United States breastfeed for up to 6 months, one estimate predicts potential healthcare savings of up to 13 billion dollars.[30] As part of a global push to improve breastfeeding rate, WHO and UNICEF implemented the baby-friendly hospital initiative (BFHI) in 1991 and has since been revised[31], which has now been widely adopted by multiple hospitals across the world. BFHI framework uses the ten steps to successful breastfeeding, which are intended to promote breastfeeding.[29][31]

Although the rates of breastfeeding are improving in the USA, there exists a racial and economic disparity. Non-Hispanic Black women have the lowest initiation rate (58%), while 80% of Hispanic/ Latino women initiate breastfeeding. Poor women breastfeed at a significantly lower rate than well-to-do mothers, and young mothers (<20 years old) breastfeed at a substantially lower rate than women over 30 years of age.[29] The rates of exclusive breastfeeding continue to drop as infants get older. Only about 41% of women are exclusively breastfeeding by three months, and a further drop to only 19% exclusively breastfed at six months.[29] The AAP points out that several critical periods exist (eg., 2-3 days, 1, 2, 3 and 4-month marks) that are at high risk of stopping or interrupting breastfeeding for various reasons, including inadequate milk supply, difficult transition to the home environment, and parental return to work at several time points.[29][32] Hence it is of extreme importance to support the family during these key periods to avoid interrupting breastfeeding. 

The only contraindications to breastfeeding are an infant with galactosemia, a mother with HIV, or a mother with active herpes simplex virus (HSV) lesions on her breast. Hepatitis is not an absolute contraindication to breastfeeding. Mothers who are febrile can continue to breastfeed. Newborns with jaundice can continue to breastfeed as well. Mothers who are using street drugs should not breastfeed, but if a mother is enrolled in a supervised opioid treatment center, then breastfeeding is encouraged. 

Donor Milk

The roots of donor breastmilk lie in the concept of wet-nurses used as far back as the ancient world until the twentieth century.[33] In some developing world countries, it is still practiced in situations when access to the mother's breastmilk is not available. In the developed world, however, donor milk is now available from donor milk banks across the USA and in many parts of the developed world. The financial impact of using donor milk is quite significant, accounting for the slow adoption in the poorer countries. The quality of the donated breastmilk varies widely from person to person.[34] Hence most centers typically use pooled donor breastmilk from multiple donors in different stages of breastfeeding, intended to limit variation in the quality of breastmilk.[35] This donor breastmilk is usually processed by centralized milk banks after screening the donors and milk samples for communicable diseases (HIV, Hepatitis B, Hepatitis C, etc.). In addition, the milk is usually sterilized by pasteurization. Most donor milk banks also require negative drug screens from the women, and the milk is screened before pooling. The processed milk is frozen using a cold-chain until it is ready to be used at the bedside. Individual institutions often have their written policy on the use of donor breastmilk.

Preterm infants, especially extremely low birth weight (ELBW) <1000 g and very low birth weight (VLBW) infants <1500 g, are at the highest need for donor breastmilk given the benefits of breastmilk over formula. While donor breastmilk is a valuable resource in the care of preterm infants, newer studies show the benefits of mother's own milk (MOM) over donor breastmilk. It is theorized that pooled pasteurized donor breastmilk has less immunogenic value due to the loss of immunoglobulins and cells during processing. Nevertheless, donor breastmilk is still regarded as superior to commercial preterm formulas, and an increasing number of neonatal intensive care units are now using donor breastmilk in their preterm infants. A survey of NICUs in the USA showed that about 45% of the NICUs are using donor breastmilk in infants up to 1800 g.[36] The DOMINO trial group studied the neurodevelopmental outcomes in preterm infants <1500 g comparing the use of donor milk versus preterm formula, which showed no differences in cognitive or neurodevelopmental scores at 18 months.[37][38] Besides, the rate of NEC was reduced from 11% to 2% in this study. Donor milk is recommended to be stopped before 36 weeks corrected age as it is too low in folate and Vitamin C (DOMINO group recommendations). An area of active research in this field involves analyzing the nutrient value of pasteurized donor breast milk, which has the potential to tailor nutrients to the specific needs of preterm infants.[39]

Formula Supplementation

Much progress has been made in the field of infant formulas. The nutritional qualities of infant formulas are closer to that of breast milk than ever before and have improved in recent years. However, active biological components (immunoglobulins, active enzymes) continue to provide a significant advantage of breast milk over formula and are actively being pursued as additives for infant formulas. A wide variety of infant formulas exist for various stages of infancy, from preterm to full-term neonates, and special situations. The regular full-term infant formulas are usually 19-20 kcal/oz, similar to breastmilk, which has an average caloric strength of 18-20 kcal/oz.

The differences between various infant formulas are primarily based on the types and amounts of proteins, carbohydrates, and fats. Proteins in infant formulas are typically cow-milk based with a predominance of casein over whey (whey-casein ratio of 20:80 compared to breastmilk (55:45 in mature milk, 80:20 in colostrum). Hydrolyzed protein formulas contain protein that has been broken down into simpler proteins and is better tolerated in infants with milk protein allergies. The protein content in amino acid-based formulas is completely broken down into amino acids. It is tolerated the best for babies with short gut syndrome, cow's milk protein intolerance, or allergies. However, debate exists on the routine use of hydrolyzed and amino acid-based formulas instead of formulas with intact protein. Partially hydrolyzed formulas have been shown in some studies to decrease the risk of atopic dermatitis.[40] The AAP committee on nutrition, section on allergy and immunology report recommends that there is not enough evidence currently available to support the routine use of partially or extensively hydrolyzed protein formulas instead of formulas with intact protein.[41][42] The choice of formula at hospital discharge is also debated among pediatricians. Based on a Cochrane review, there is a lack of data on discharge formula for a NICU graduate infant. About 78% of neonatologists do not give HMF on discharge to exclusively breastfed babies. The increase in length with 22 calorie formula on discharge is marginal with little effect on HC.

Summary/Learning Points

• Optimal nutrition with the right balance of various nutritional components is essential for optimal growth.
• Growth is best monitored using serial measurements of weight, length, and head circumference on the appropriate growth charts (CDC vs. WHO growth charts, Fenton for preterm infants until corrected to 50 weeks, and special charts for exceptional circumstances). 
• The AAP recommends exclusive breastfeeding for the first six months of life and up to 4-6 months in certain conditions.
• Mother's milk is preferred over donor milk for the best outcomes. However, in the absence of the mother's milk, infants <1500 g definitively benefit from the use of pasteurized donor human milk. The use of donor milk is currently subject to institutional and local policies and procedures.

Clinical Significance

Stunted growth is associated with poor neurodevelopmental outcomes. Although improved early growth is associated with better cognitive results, there might be a trade-off in terms of worse metabolic results.[6] Accelerated growth in the postnatal period is a trigger for adult disease.[2] Middle-aged adults born with a low weight present a higher prevalence of diabetes and obesity and also higher leptin levels and leptin to fat mass ratio than adults born with a healthy weight; therefore, those born with a low weight should be counseled regarding the risks of developing diabetes and cardiovascular disease.[3] 

Ultimately we know adequate nutrition is imperative for survival. Still, the intricacies in the balancing act between providing sufficient protein, carbohydrates, fats, and micronutrients while not predisposing the individual to an increased risk of developing long term complications are delicate.

Enhancing Healthcare Team Outcomes

Ensuring neonates and infants receive appropriate nutrition in the hospital and outpatient setting necessitates a team-based approach. The pediatrician, gastroenterologist, NP, PA, or nurse would first gain an understanding of the child's overall health, feeding regimen and schedule, and any concerns the parent might have through the interview and history-taking. The nurse would meticulously measure the infant's growth parameters as accurate measurements are vital, and the team would compare them with previous measurements to determine if the infant is receiving adequate feedings.

If the child is being breastfed and there are parental concerns with breastfeeding techniques, the team could refer to a lactation consultant who would be able to offer guidance to the parent by evaluating their current method and providing education and support. If the quantity of feeds is an issue, the health providers will work with the parent to make a plan that sets feeding and weight goals for the infant. For infants receiving commercial formula, the team may also recommend fortification with iron and supplementation with vitamin D and either order and administer these in the inpatient setting or provide prescriptions for these nutrients for the parents to fill at the pharmacy.[43]