FAQ's in Preterm Care and Nutrition Answered by Experts

Feeding option in the preterm neonate is decided on the basis of:

• Gestational age at birth or birth weight.
• Presence of euective sucking, swallowing, and coordination between suck, swallow, & respiration.
• Presence or absence of risk factor for necrotizing enterocolitis (NEC).

Apart from usefulness and advantages of human milk in term and preterm neonates, additional benefits that human milk provides to this highly vulnerable preterm population include:

• Prevention of NEC
• Prevention of allergies and other atopic diseases
• Prevention of bronchopulmonary dysplasia (BPD)
• Prevention of retinopathy of prematurity
• Better neurodevelopmental outcomes
• Other benefits

include decreased rates of late-onset sepsis, fewer re-hospitalizations in the first year of life, lower rates of metabolic syndrome, lower blood pressure and low-density lipoprotein levels, and less insulin and leptin resistance when they reach adolescence, as compared to premature infants receiving formula.

Human milk is recommended for all neonates, including preterm infants, for the first 6 months of corrected age exclusively, but unfortified human milk may not meet the recommended daily allowances for preterm infants, which are as follows: Enteral fluid intake of 135–200 ml/kg/day,energy intake of 110–135 Kcal/kg/day, and protein intake of 3.5 to 4.5 g/kg/day.

The use of human milk fortifier (HMF) helps meet the additional high nutritional requirements in infants with:

• Calcium and phosphate deficits leading to higher risk of low bone mineralization, metabolic bone diseases, and slow skeletal growth compared to infants born at term
• Nutritional deficiency and growth restriction both in utero and in the early postnatal period,as they may have long-term metabolic and cardiovascular consequences
• Very low birth weight (VLBW), as they may develop delays in growth and nutritional deficits

Studies have shown that the addition of HMF is associated with short-term improvements in weight, height, bone mineralization, neurologic outcome, and head growth.

Recommendation for HMF: Whom to start

The use of human milk fortifier (HMF) helps meet the additional high nutritional requirements in infants with:

• As per the National Neonatology Forum, India, Evidence Based Clinical Practice Guidelines (2010) and World Health Organization, HMF is added to human milk in infants < 32 weeks or <1500 g who fail to gain adequate weight at full feed of 180–200 ml/kg/day.
• Since contemporary clinical practice sees a very high percentage of preterm VLBW babies suffering from extrauterine growth restriction (EUGR), multicomponent fortification is started in all preterm neonates with birth weight <1800 g.

When to start HMF: At our center, we start fortification with bovine-based HMF when baby reaches 100 ml/kg/day of feed. Human milk based HMF is not available in India and is very expensive to import.

How long:There is no worldwide consensus on how long should fortification be continued; however, at most centers, fortifiers are discontinued when the weight of the baby reaches 2 kg. Our center has policy to continue fortification till baby is on tube, paladai, or bottle feeds and had reached or crossed the birth percentile or is on direct breast feeds, in which case other supplements (like Ca/P/Iron/Vit D) are added as drugs.

The main concern regarding enteral feeding is the presumed association of enteral feeding with NEC and feed intolerance. Observational studies and systemic review showed that delayed introduction and slow advancement of enteral feed decreases the risk of NEC and feed intolerance. However, disadvantages of delaying enteral feeding include delay in functional adaptation of the gastrointestinal tract and prolong the need for parenteral nutrition with its attendant infectious and metabolic risks.
Suggested enteral feeding protocols

Modified fluid regimen for a neonate during the first week will be as follows: Maintenance fluid (1st week): Urine output + Insensible losses – 1%–2% of birth weight. Desired urine output is dependent upon solute load required to be excreted.

Source: Dell KM. Chapter 44: Fluid, Electrolytes, and Acid-Base Homeostasis. In: Martin RJ , Fanaroff AA, Walsh MC. (eds.) Fanaroff and Martin's Neonatal-Perinatal Medicine. Diseases of the Fetus and Infant. 9th edition. Volume 1. Philadelphia, PA: Elsevier health sciences; 2015. Pg. 615.

Infants with a birth weight of 1250–1500 g regained their birth weight faster with 3-hourly feeding than with 2-hourly feeding

Our approach to preterm with AREDF: If the abdominal examination is normal, start enteral feeding 10-20 ml/kg/day starting on day 2 of life strictly on mother’s milk or donor human milk but progressive feed 30–40 ml/kg/day from day 3–4 of life has been found safe. More caution is needed while feeding small for gestational age SGA babies with AREDF and gestation <29 weeks.

Docosahexaenoic acid (DHA) is a long chain poly- unsaturated fatty acid (LCPUFA) that has a role in the cognitive and visual development, as well as in the immune function of newborns. Premature infants, especially those born before 30 weeks, have been shown to have a deficit in DHA shortly after delivery for several reasons, including foregoing third trimester DHA accretion, receiving enteral breast milk or donor milk feeds that are typically low in DHA, and having an increased risk of requiring prolonged total parenteral nutrition.

The addition of LCPUFAs has both theoretical and potential clinical benefit. A recent study of preterm infants of 24–32 weeks of gestational age using early and near-term magnetic resonance imaging and red blood cell membrane fatty acid composition showed that higher DHA and lower linoleic acid (LA) levels in the first few postnatal weeks were associated with decreased intraventricular hemorrhage, improved microstructural brain development, and improved neurodevelopmental outcomes.

For a neonate <33 weeks on birth, anthropometry is plotted on revised Fenton chart 2013 and continued to be plotted till 50 weeks postmenstrual age (PMA). But with the advent of intergrowth chart, which actually represents the population of both developed and developing countries, many institutes have started using this chart for growth monitoring till 64 weeks PMA and then WHO chart till 5 years of age.

The nutrient requirements for preterm infants that were used to develop the preterm formulas were based on the reference fetus defined by Ziegler et al. and fetal body composition data by Widdowson et al. Preterm formulas were developed to meet high protein, energy, and mineral requirements that were considered necessary to support a rate of growth in the preterm VLBW infant that would approximate with that of the normal healthy growing fetus in the third trimester of intrauterine life.

• Fat: Source is blend of vegetable oils, including DHA: ARA (arachidonic acid) and medium chain triglycerides (MCTs). DHA and ARA in a ratio of 1:1 or 1:2 are used for optimal neurodevelopmental outcome. LCPUFAs have been added in amounts similar to those in human milk, producing higher tissue concentrations and reportedly better visual acuity.
• Carbohydrate: Source is a combination of lactose and sucrose. The recent preterm formulas replace sucrose with relatively easily digestible low osmolar glucose polymers. Nevertheless, lactose remains important for normal nutrition and, especially, for the prevention of NEC by promoting the growth of bifido- and lactobacillus organisms and suppressing the growth of opportunistic bacteria by lowering distal intestinal pH. Therefore, it remains an important constituent of the preterm formulas.
• Protein: Source is cows milk. Whey now predominates as the main protein rather than casein. Whey protein is more digestible than casein, and its use as markedly reduced the development of lactobezoars. The newer 60% whey to 40% casein composition ratio produces more rapid gastric emptying, digestion, and amino acid absorption, as well as less metabolic acidosis.
• Minerals: Preterm formulas also are designed with much higher contents of sodium and potassium to compensate for renal losses characteristic of preterm infants with limited renal solute conservation capacity. Calcium and phosphorus contents are also higher to help promote bone mineralization.
• Vitamins: The levels of vitamins are higher in preterm formulas (vitamins A and E) to compensate for more limited fat absorption in these infants and to help counter the many inflammatory conditions these infants experience. Even with these higher contents, vitamins A and D especially might require additional supplementation.
• Micronutrients: Most micronutrients are adequately provided by preterm formulas, but 1.8 mg/100 kcal of iron contained in many preterm formulas might not be sufficient for rapidly growing preterm infants, who are not transfused.

Despite the higher mineral and vitamin contents of preterm formulas, most products have relatively safe osmolalities, from 210 to 220 mOsm/L at 20 kcal/oz to 250–270 mOsm/L at 24 kcal/oz. Preterm formulas are used in preterm infants whose mothers are unable to express sufficient milk for full enteral feeding, supplemented or not, or when fortified donor human milk is not available. While preterm formulas improve neurodevelopmental outcomes compared to term formulas and unfortified donor milk, they do not produce neurodevelopmental outcomes better than fortified human milk.

The American Academy of Paediatrics recommends the goal for extrauterine growth to parallel the intrauterine growth trajectory of the fetus at a comparable gestational age. EUGR is defined as having a measured growth parameter (weight, length, or head circumference) that is ≤10th percentile of intrauterine growth expectation based on estimated PMA in premature (23–34 weeks estimated gestational age) neonates at the time of hospital discharge. The incidence of postnatal growth failure in VLBW infants ranges between 43% and 97% in various centers.
Also, VLBW infants are born with a multitude of nutritional disadvantages that place them at a high risk for EUGR. The VLBW infant has high metabolic needs and limited nutritional stores of protein, fat, and minerals to meet the demands of extrauterine life, making this goal difficult to achieve. EUGR is associated with an increased risk of poor neurodevelopmental outcome. Inadequate postnatal nutrition is an important factor contributing to growth failure, as most very preterm infants experience major protein and energy deficits during neonatal intensive care unit hospitalization. First-week protein and energy intakes are associated with 18-month developmental outcomes in very preterm infants. Early aggressive nutrition, including parenteral and enteral, is well tolerated in the very preterm infant and is effective in improving growth. Continued provision of appropriate nutrition (fortified human milk or premature formula) is important throughout the growing care during the hospitalization. After discharge, exclusively breast-fed infants require additional supplementation.